Database technologies for l-system simulations in virtual plant applications on bioinformatics

One of the most important advantages of database systems is that the underlying mathematics is rich enough to specify very complex operations with a small number of statements in the database language. This research covers an aspect of biological informatics that is the marriage of information technology and biology, involving the study of real-world phenomena using virtual plants derived from L-systems simulation. L-systems were introduced by Aristid Lindenmayer as a mathematical model of multicellular organisms. Not much consideration has been given to the problem of persistent storage for these simulations. Current procedures for querying data generated by L-systems for scientific experiments, simulations and measurements are also inadequate. To address these problems the research in this paper presents a generic process for data-modeling tools (L-DBM) between L-systems and database systems. This paper shows how L-system productions can be generically and automatically represented in database schemas and how a database can be populated from the L-system strings. This paper further describes the idea of pre-computing recursive structures in the data into derived attributes using compiler generation. A method to allow a correspondence between biologists' terms and compiler-generated terms in a biologist computing environment is supplied. Once the L-DBM gets any specific L-systems productions and its declarations, it can generate the specific schema for both simple correspondence terminology and also complex recursive structure data attributes and relationships.

Autosomal dominant hypocalcemia: A novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor

We report a novel activating mutation (E604K) of the calcium-sensing receptor in a family with autosomal dominant hypocalcemia. Whereas all affected individuals exhibited marked hypocalcemia, some cases with untreated hypocalcemia exhibited seizures in infancy, whereas others were largely asymptomatic from birth into adulthood. The missense mutation E604K (G2182A, GenBank accession no. U20759), which affects an amino acid residue in the C terminus of the cysteine-rich domain of the extracellular head, co-segregated with hypocalcemia in all seven individuals for whom DNA was available. Two unaffected, normocalcemic members of the family did not exhibit the mutation. The molecular impact of the mutation on two key components of the signaling response was assessed in HEK-293 cells transiently transfected with cDNA corresponding to either the wild-type calcium-sensing receptor or the E604K mutation derived by site-directed mutagenesis. There was a significant leftward shift in the concentration response curves for the effects of extracellular Ca2+ on both intracellular Ca2+ mobilization (determined by aequorin luminescence) and MAPK activity (determined by luciferase expression). The C terminus of the cysteine-rich domain of the extracellular head may normally act to suppress receptor activity in the presence of low extracellular Ca2+ concentrations.

Chapter 16: Prophylactic Human Papillomavirus Vaccines

Candidate prophylactic vaccines based on papillomavirus L1 virus-like particles (VLPs) are currently in human clinical trials. The main long-term goal of the vaccine is to reduce the incidence of cervical cancer and its precursors. In animal papillomavirus models, systemic immunization with L1 VLPs can induce high titers of neutralizing antibodies that confer protection against high-dose experimental papillomavirus challenge. In humans, systemic vaccination with L1 VLPs has been well tolerated and induced high serum antibody titers (at least 40 times higher than titers seen following natural infection). A recent proof of principle HPV16 L1 VLP efficacy trial has shown excellent protection against persistent HPV16 infection and associated cytological abnormalities. Large scale efficacy trials of L1 VLPs from HPV16 and 18 (the HPV types found most frequently in cervical cancer), with or without HPV6 and 11 (the HPV types responsible for most genital warts), are planned. If the results of these large trials support the encouraging results of the early trials, they should lead to a commercial prophylactic HPV vaccine. Implementation issues may include how to make the vaccine available in the developing world, where the majority of cervical cancer cases occur, the appropriate age of vaccination, and the role of male vaccination. Because a VLP vaccine is likely to provide type-specific protection, increasing the number of cancer-associated HPV types in the vaccine is a likely approach to broadening the protection to additional types. There will probably also be efforts to develop alternative vaccine formulations better suited to implementation in developing countries as well as attempts to develop vaccines with a therapeutic activity against established HPV infection because a combined prophylactic/therapeutic vaccine may be expected to have an even greater impact than a purely prophylactic vaccine on HPV induced disease.

Parathyroid hormone venous sampling prior to reoperation for primary hyperparathyroidism

Background: The surgical cure rate for primary hyperparathyroidism is greater than 95%. For those who have recurrent or persistent disease, preoperative localization improves reoperation success rates. Selective parathyroid venous sampling (SPVS) for intact parathyroid hormone is particularly useful when non-invasive localization techniques are negative or inconclusive. Methods: We present all known cases (n = 13) between 1994 and 2002 who had venous sampling for localization at our institution prior to reoperation for recurrent or persistent primary hyperparathyroidism. Comparison was made with non-invasive localization procedures. Results of invasive and non-invasive localization were correlated with surgical findings. Results: Of the nine reoperated cases, eight had positive correlations between SPVS and operative findings and histopathology. SPVS did not reveal the parathyroid hormone source in one case with negative non-invasive localization procedures. Comparisons between SPVS, computerized tomography (CT), and parathyroid scintigraphy (MIBI) as expressed in terms of true positive (TP), false positive (FP) and false negative (FN) were: SPVS - TP 88.8%, FP 0%, FN 11.1%; CT - TP 22.2%, FP 22.2%, FN 55.5%; and MIBI - TP 33.3%, FP 0%, FN 66.6%. At least seven of the nine operated cases have been cured; another remained normocalcaemic 2 weeks after subtotal parathyroidectomy. Conclusion: In our institution SPVS has proven to be a valuable tool in cases with recurrent or persistent primary hyperparathyroidism and negative non-invasive localization procedures.

Cortex, cognition and the cell: New insights into the pyramidal neuron and prefrontal function

Arguably the most complex conical functions are seated in human cognition, the how and why of which have been debated for centuries by theologians, philosophers and scientists alike. In his best-selling book, An Astonishing Hypothesis: A Scientific Search for the Soul, Francis Crick refined the view that these qualities are determined solely by cortical cells and circuitry. Put simply, cognition is nothing more, or less, than a biological function. Accepting this to be the case, it should be possible to identify the mechanisms that subserve cognitive processing. Since the pioneering studies of Lorent de No and Hebb, and the more recent studies of Fuster, Miller and Goldman-Rakic, to mention but a few, much attention has been focused on the role of persistent neural activity in cognitive processes. Application of modern technologies and modelling techniques has led to new hypotheses about the mechanisms of persistent activity. Here I focus on how regional variations in the pyramidal cell phenotype may determine the complexity of cortical circuitry and, in turn, influence neural activity. Data obtained from thousands of individually injected pyramidal cells in sensory, motor, association and executive cortex reveal marked differences in the numbers of putative excitatory inputs received by these cells. Pyramidal cells in prefrontal cortex have, on average, up to 23 times more dendritic spines than those in the primary visual area. I propose that without these specializations in the structure of pyramidal cells, and the circuits they form, human cognitive processing would not have evolved to its present state. I also present data from both New World and Old World monkeys that show varying degrees of complexity in the pyramidal cell phenotype in their prefrontal cortices, suggesting that cortical circuitry and, thus, cognitive styles are evolving independently in different species.

Magnetic polarization currents in double quantum dot devices

We investigate coherent electron transport through a parallel circuit of two quantum dots (QDs), each of which has a single tunable. energy level. Electrons tunnelling via each dot from the left lead interfere with each other at the right lead. It is shown that due to the quantum interference of tunnelling electrons the double QD device is magnetically polarized by coherent circulation of electrons on the closed path through the dots and the leads. By varying the energy level of each dot one can make the magnetic states of the device be up-, non- or down-polarized. It is shown that for experimentally accessible temperatures and applied biases the magnetic polarization currents Should be sufficiently large to observe with current nanotechnology.