The potential role of environmental exposures and genomic signaling in development of central nervous system tumors

The etiology of central nervous system tumors (CNSTs) is mainly unknown. Aside from extremely rare genetic conditions, such as neurofibromatosis and tuberous sclerosis, the only unequivocally identified risk factor is exposure to ionizing radiation, and this explains only a very small fraction of cases. Using meta-analysis, gene networking and bioinformatics methods, this dissertation explored the hypothesis that environmental exposures produce genetic and epigenetic alterations that may be involved in the etiology of CNSTs. A meta-analysis of epidemiological studies of pesticides and pediatric brain tumors revealed a significantly increased risk of brain tumors among children whose mothers had farm-related exposures during pregnancy. A dose response was recognized when this risk estimate was compared to those for risk of brain tumors from maternal exposure to non-agricultural pesticides during pregnancy, and risk of brain tumors among children exposed to agricultural activities. Through meta-analysis of several microarray studies which compared normal tissue to astrocytomas, we were able to identify a list of 554 genes which were differentially expressed in the majority of astrocytomas. Many of these genes have in fact been implicated in development of astrocytoma, including EGFR, HIF-1α, c-Myc, WNT5A, and IDH3A. Reverse engineering of these 554 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme (GBM) were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. Lastly, bioinformatics analysis of environmental databases and curated published results on GBM was able to identify numerous potential pathways and geneenvironment interactions that may play key roles in astrocytoma development. Findings from this research have strong potential to advance our understanding of the etiology and susceptibility to CNSTs. Validation of our ‘key genes’ and pathways could potentially lead to useful tools for early detection and novel therapeutic options for these tumors.

Infection of the central nervous system by Mycobacterium tuberculosis in patients infected with human immunodeficiency virus (the new neurotuberculosis)

Neurologic complications of HIV infection are numerous. This review focuses on the clinical presentation, diagnostic particularities and therapeutic issues of neurotuberculosis. The pertinent literature describing this important infection is succinctly summarized with a particular emphasis on the discussion of differences in clinical presentation between HIV-infected and -uninfected patients.

The effect of radiation on the electron pairing in a multiband system

The possible occurrence of a generalized (1-wave) nonequilibrium superconducting state in a multiband system under certain conditions is studied. In the model the radiation field causes interband mixing, and phonons of an appropriate mode (branch) are involved in the interband scattering of electrons of two conduction bands of the system. The strength of the generalized 1-wave pairing interaction between quasiparticles belonging to new radiation admixed states depends on the density (n o/V) of quanta in the system. The coupling constant has the form Xl= AiB(n o/V)/[C + B(no/V)], where A1, B, and C are parameters. For C > B(n0/V), the transition temperature T1* increases with (no/V) in the initial stages. It levels off with higher power. With further increase of power, the transition temperature is expected to drop sharply due to heating effects which cause pair breaking. Estimates show that p-wave (triplet state) pairing may be possible under radiation-induced nonequilibrium situations in appropriate systems. Estimates for lifetimes of various processes quasiparticle, phonon, pair relaxation, and photon-induced mixing) show that the coherence required for the mixing and pairing effects will be maintained for the temperature range and photon density considered.

Effect of position on precision within the recording field of a markerless motion capture system

Introduction Markerless motion capture systems are relatively new devices that can significantly speed up capturing full body motion. A precision of the assessment of the finger’s position with this type of equipment was evaluated at 17.30 ± 9.56 mm when compare to an active marker system [1]. The Microsoft Kinect was proposed to standardized and enhanced clinical evaluation of patients with hemiplegic cerebral palsy [2]. Markerless motion capture systems have the potential to be used in a clinical setting for movement analysis, as well as for large cohort research. However, the precision of such system needs to be characterized. Global objectives • To assess the precision within the recording field of the markerless motion capture system Openstage 2 (Organic Motion, NY). • To compare the markerless motion capture system with an optoelectric motion capture system with active markers. Specific objectives • To assess the noise of a static body at 13 different location within the recording field of the markerless motion capture system. • To assess the smallest oscillation detected by the markerless motion capture system. • To assess the difference between both systems regarding the body joint angle measurement. Methods Equipment • OpenStage® 2 (Organic Motion, NY) o Markerless motion capture system o 16 video cameras (acquisition rate : 60Hz) o Recording zone : 4m * 5m * 2.4m (depth * width * height) o Provide position and angle of 23 different body segments • VisualeyezTM VZ4000 (PhoeniX Technologies Incorporated, BC) o Optoelectric motion capture system with active markers o 4 trackers system (total of 12 cameras) o Accuracy : 0.5~0.7mm Protocol & Analysis • Static noise: o Motion recording of an humanoid mannequin was done in 13 different locations o RMSE was calculated for each segment in each location • Smallest oscillation detected: o Small oscillations were induced to the humanoid mannequin and motion was recorded until it stopped. o Correlation between the displacement of the head recorded by both systems was measured. A corresponding magnitude was also measured. • Body joints angle: o Body motion was recorded simultaneously with both systems (left side only). o 6 participants (3 females; 32.7 ± 9.4 years old) • Tasks: Walk, Squat, Shoulder flexion & abduction, Elbow flexion, Wrist extension, Pronation / supination (not in results), Head flexion & rotation (not in results), Leg rotation (not in results), Trunk rotation (not in results) o Several body joint angles were measured with both systems. o RMSE was calculated between signals of both systems. Results Conclusion Results show that the Organic Motion markerless system has the potential to be used for assessment of clinical motor symptoms or motor performances However, the following points should be considered: • Precision of the Openstage system varied within the recording field. • Precision is not constant between limb segments. • The error seems to be higher close to the range of motion extremities.

PAMAM Dendrimer-Drug Interactions: Effect of pH on the Binding and Release Pattern

Understanding the dendrimer-drug interaction is of great importance to design and optimize the dendrimer-based drug delivery system. Using atomistic molecular dynamics (MD) simulations, we have analyzed the release pattern of four ligands (two soluble drugs, namely, salicylic acid (Sal), L-alanine (Ala), and two insoluble drugs, namely, phenylbutazone (Pbz) and primidone (Prim)), which were initially encapsulated inside the ethylenediamine (EDA) cored polyamidoamine (PAMAM) dendrimer using the docking method. We have computed the potential of mean force (PMF) variation with generation 5 (G5)-PAMAM dendrimer complexed with drug molecules using umbrella sampling. From our calculated PMF values, we observe that soluble drugs (Sal and Ala) have lower energy barriers than insoluble drugs (Pbz and Prim). The order of ease of release pattern for these drugs from G5 protonated PAMAM dendrimer was found to be Ala > Sal > Prim > Pbz. In the case of insoluble drugs (Prim and Pbz), because of larger size, we observe much nonpolar contribution, and thus, their larger energy barriers can be reasoned to van der Waals contribution. From the hydrogen bonding analysis of the four PAMAM drug complexes under study, we found intermolecular hydrogen bonding to show less significant contribution to the free energy barrier. Another interesting feature appears while calculating the PMF profile of G5NP (nonprotonated)-PAMAM Pbz and G5NP (nonprotonated)-PAMAM-Sal complex. The PMF was found to be less when the drug is bound to nonprotonated dendrimer compared to the protonated dendrimer. Our results suggest that encapsulation of the drug molecule into the host PAMAM dendrimer should be carried out at higher pH values (near pH 10). When such complex enters the human body, the pH is around 7.4 and at that physiological pH, the dendrimer holds the drug tightly. Hence the release of drug can occur at a controlled rate into the bloodstream. Thus, our findings provide a microscopic picture of the encapsulation and controlled release of drugs in the case of dendrimer-based host-guest systems.

Effect of Pt on interdiffusion and mechanical properties of the gamma and gamma ` phases in the Ni-Pt-Al system

The effect of Pt on the growth kinetics of the gamma'-Ni(Pt)](3)Al ordered intermetallic phase and the gamma- Ni(Pt, Al) solid solution diffusion rates of the species, hardness and elastic modulus was examined by employing the diffusion couple experimental technique. Experiments were conducted by using the beta-Ni(Pt)Al phase and Ni(Pt) alloy couples, each of which had a fixed amount of Pt (5, 10 and 15 at. %) in both the end members so that the Pt content is more or less constant throughout the interdiffusion zone. The results suggest that the growth kinetics of both phases and the average effective interdiffusion coefficients of Ni and Al increase with the increase in Pt content. Nanoindentation studies across the compositional gradients show that the mechanical properties of the intermetallic phase in the superalloy are relatively insensitive to the presence of Pt but are more sensitive to the Ni/Al ratio. In contrast, the marked variation in the hardness of the gamma phase were noted, increasing markedly with Al concentration in a given couple and also increasing with increasing Pt content. Possible causes for the observed variations are discussed.

Effect of phases on the dynamic evolution of a Lambda system with spontaneously generated coherence

The dynamic evolution of a A system coupled by two strong coherent fields is investigated by taking spontaneously generated coherence (SGC) into account. By numericaly simulation, it is shown that the relative phase of the two coherent fields affects significantly the time scale to the coherent population trapping state. In addition, an analytical expression to the evolution rate which is consistent with the numerical results is given. (c) 2005 Elsevier B.V. All rights reserved.

The effect of KSCN on the partition of proteins in polyethylene glycol/(NH4)(2)SO4 aqueous two-phase system

The effect of potassium thiocyanate on the partitioning of lysozyme and BSA in polyethylene glycol 2000/ammonium sulfate aqueous two-phase system has been investigated. As a result of the addition of potassium thiocyanate to the PEG/ammonium sulfate system, the PEG/mixed salts aqueous two-phase system was formed. It was found that the potassium thiocyanate could alter the pH difference between the two phases, and, thus, influence the partition coefficients of the differently charged proteins. The relationship between partition coefficient of the proteins and pH difference between two phases has been discussed. It was proposed that the pH difference between two phases could be employed as the measurement of electrostatic driving force for the partitioning of charged proteins in polyethylene glycol 2000/ammonium sulfate aqueous two-phase system.

Mice lacking alpha-tocopherol transfer protein gene have severe alpha-tocopherol deficiency in multiple regions of the central nervous system

Ataxia with vitamin E deficiency is caused by mutations in a-tocopherol transfer protein (a-TTP) gene and it can be experimentally generated in mice by a-TTP gene inactivation (a-TTP-KO). This study compared a-tocopherol (a-T) concentrations of five brain regions and of four peripheral organs from 5 months old, male and female, wild-type (WT) and a-TTP-KO mice. All brain regions of female WT mice contained significantly higher a-T than those from WT males. a-T concentration in the cerebellum was significantly lower than that in other brain regions of WT mice. These sex and regional differences in brain a-T concentrations do not appear to be determined by a-TTP expression which was undetectable in all brain regions. All the brain regions of a-TTP-KO mice were severely depleted in a-T. The concentration of another endogenous antioxidant, total glutathione, was unaffected by gender but was decreased slightly but significantly in most brain regions of a-TTP-KO mice. The results show that both gender and the hepatic a-TTP, but not brain a-TTP gene expression are important in determining a-T concentrations within the brain. Interestingly, functional abnormality (ataxia) develops only very late in a-TTP-KO mice in spite of the severe a-tocopherol deficiency in the brain starting at an early age.