Nevoscopy: three-dimensional computed tomography of nevi and melanomas in situ by transillumination

The thickness of a malignant nevus has been found to be an important prognostic factor for patients with melanoma. We have designed a new method of imaging nevi that permits their thickness to be measured in situ. Using fiber optics directed into the surrounding skin, we transilluminate the nevus. Three images are picked up by a digitizing TV camera: the vertical image (90 degrees ), a glancing image (180 degrees ), and one at 45 degrees , obtained by using two front-silvered mirrors held next to the nevus in a "nevoscope." The digitized images are used in a computed tomography algorithm to calculate approximate vertical cross sections of the nevus. The algorithm is one we recently developed to permit reconstruction from a very few projections. Our method is completely noninvasive. It may be used to check all the nevi on a patient. Without excisions, we could establish a baseline three-dimensional shape for each nevus, follow any changes in time, and obtain an early warning of increase in thickness and possible malignancy.     

In vitro growth and drug sensitivity of tumor colony-forming units from human tumor xenografts

To investigate the feasibility of using tissue obtained from human tumor xenografts for in vitro screening of antineoplastic agents, we grew human tumor colony-forming units (CFU) in semisold agar from xenografts serially passaged in nude mice. Growth of human tumor CFU was accomplished from nine xenografts representing five different histological tumor types (ovarian carcinoma, adenocarcinoma of the colon, malignant melanoma, epidermoid carcinoma of the lung, and malignant astrocytoma). Cloning efficiency ranged from 0.04 to 0.1% and showed significant variability both between tumor types and between individual animals bearing the same type of xenograft. A high percentage of tumor CFU was in S phase [47 +/- 20% (S.D.)] as determined by the thymidine "suicide" technique. The number of tumor CFU observed increased linearly with increasing numbers of cells plated. In vitro drug sensitivity of the tumor CFU was assessed to Adriamycin, cis-platinum, and melphalan. The patterns of drug sensitivity were found to be reproducible and stable over a period of 9 months. Drug sensitivity curves to Adriamycin for five xenografts representing four tumor types showed complex patterns with plateau portions similar to those described for tumor CFU from primary tumors. The rank order of sensitivity of the tumors was compared to that of normal granulocyte-macrophage progenitors and, with the exception of the melanomas, was found to correlate well with clinical experience (order of sensitivity = colon less than ovary less than bone marrow). Growth of human tumor CFU from xenografts represents a reproducible and stable means for the study of the biology of tumor CFU and has potential applications as a means for screening new anticancer agents.     

Propagation dynamics of ultra-short high-power laser pulses in air: supercontinuum generation and transverse ring formation

Numerical and semi-analytical results of the propagation of high-power ultra-short near IR laser pulses propagating in ionizing air are presented.     

Minimising total cost with regular and emergency outsourcing sources: a neuro-dynamic programming approach

This study models and explains the business situation of an organisation which has regular and emergency outsourcing sources and where decisions have to be made at the beginning of every period regarding how much to order from these sources, so as to balance between different cost components of current and future periods. Previous works in this area have tried to attack this problem with dynamic programming. In this project, neuro-dynamic programming has been applied, and the reasons for doing so have been clearly stated. This model not only derives policies in order to minimise the expected total discounted cost over a period of time, but also enables the system to learn to make such decisions, and to improve its actions by using reinforcement learning. The performance of the present work has been measured quantitatively and has been compared with the models stated in literature. This study will be very useful for the organisations where such business problems exist or are likely to exist. This study will also be of great use to researchers, who are keen to understand and model the given business situation with distribution independent demand based models.     

Growth rate characteristics of acoustic neuromas associated with neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is a dominantly inherited disorder characterized by the occurrence of bilateral acoustic neuromas (ANs and other central nervous system tumors. Magnetic resonance images and audiologic data on 22 patients with NF2 who underwent multiple studies at the National Institutes of Health between 1983 and 1993 were reviewed to determine the growth characteristics of ANs in these patients. The average growth rate of ANs in NF2 patients was 0.30 cm3 per year and was significantly higher in older patients (0.75 cm3 per year) than in younger ones (0.12 cm3 per year). Larger ANs were more commonly found in patients with concomitant spinal tumors or meningiomas. NF2 patients with spinal tumors but not meningiomas demonstrated faster growth rates than patients without additional tumor burden. The data from this study suggest that older patients or patients with associated spinal tumors have faster growing ANs and therefore should be followed closely and treated aggressively.     

New protein genetic studies in six Amazonian Indian populations

A total of 732 individuals affiliated with six Amazonian Indian populations were variously studied in relation to 26 protein genetic systems. Eleven of them were found to be monomorphic in these groups, in accordance with previous investigations. Similarities and dissimilarities (the latter involving the Rh, Duffy, haptoglobin and transferrin systems) were observed in relation to earlier investigations in four of these populations (Galibi, Palikour, Mundurucu and Tenharim). A dimeric, cathodal variant of albumin was found among two Galibi subjects, and the fairly common occurrence of CP* ACAY among some South American Indian populations was confirmed. The results in the six populations were compared with those from 29 others. When relationships are searched for among tribes of the same linguistic group, the factor that seems to be most influential is geographical localization, an exception being the pattern observed among the Cayapo subgroups. The latter shows genetic differences of the same level of magnitude as those observed among Ge-speaking tribes.     

Cleavage motifs of the yeast 20S proteasome beta subunits deduced from digests of enolase 1

The 436-amino acid protein enolase 1 from yeast was degraded in vitro by purified wild-type and mutant yeast 20S proteasome particles. Analysis of the cleavage products at different times revealed a processive degradation mechanism and a length distribution of fragments ranging from 3 to 25 amino acids with an average length of 7 to 8 amino acids. Surprisingly, the average fragment length was very similar between wild-type and mutant 20S proteasomes with reduced numbers of active sites. This implies that the fragment length is not influenced by the distance between the active sites, as previously postulated. A detailed analysis of the cleavages also allowed the identification of certain amino acid characteristics in positions flanking the cleavage site that guide the selection of the P1 residues by the three active beta subunits. Because yeast and mammalian proteasomes are highly homologous, similar cleavage motifs might be used by mammalian proteasomes. Therefore, our data provide a basis for predicting proteasomal degradation products from which peptides are sampled by major histocompatibility complex class I molecules for presentation to cytotoxic T cells.