MeV ion beam lithography of biocompatible halogenated Parylenes using aperture masks

Parylenes are poly(p-xylylene) polymers that are widely used as moisture barriers and in biomedicine because of their good biocompatibility. We have investigated MeV ion beam lithography using 16O+ ions for writing defined patterns in Parylene-C, which is evaluated as a coating material for the Cochlear Implant (CI) electrode array, a neuroprosthesis to treat some forms of deafness. Parylene-C and -F on silicon and glass substrates as well as 50 μm thick PTFE were irradiated to different fluences (1×1013-1×10161×1013-1×1016 1 MeV 16O+ ions cm−2) through aperture masks under high vacuum and a low pressure (<10−3 mbar) oxygen atmosphere. Biocompatibility of the irradiated and unirradiated surfaces was tested by cell-counting to determine the proliferation of murine spiral ganglion cells. The results reveal that an oxygen ion beam can be used to pattern Parylene-C and -F without using a liquid solvent developer in a similar manner to PTFE but with a ∼25× smaller removal rate. Biocompatibility tests showed no difference in cell adhesion between irradiated and unirradiated areas or ion fluence dependence. Coating the Parylene surface with an adhesion-promoting protein mixture had a much greater effect on cell proliferation.

Ion channel macromolecular complexes in cardiomyocytes: roles in sudden cardiac death.

The movement of ions across specific channels embedded on the membrane of individual cardiomyocytes is crucial for the generation and propagation of the cardiac electric impulse. Emerging evidence over the past 20 years strongly suggests that the normal electric function of the heart is the result of dynamic interactions of membrane ion channels working in an orchestrated fashion as part of complex molecular networks. Such networks work together with exquisite temporal precision to generate each action potential and contraction. Macromolecular complexes play crucial roles in transcription, translation, oligomerization, trafficking, membrane retention, glycosylation, post-translational modification, turnover, function, and degradation of all cardiac ion channels known to date. In addition, the accurate timing of each cardiac beat and contraction demands, a comparable precision on the assembly and organizations of sodium, calcium, and potassium channel complexes within specific subcellular microdomains, where physical proximity allows for prompt and efficient interaction. This review article, part of the Compendium on Sudden Cardiac Death, discusses the major issues related to the role of ion channel macromolecular assemblies in normal cardiac electric function and the mechanisms of arrhythmias leading to sudden cardiac death. It provides an idea of how these issues are being addressed in the laboratory and in the clinic, which important questions remain unanswered, and what future research will be needed to improve knowledge and advance therapy.

MINERALOCORTICOID REGULATION OF ION CONDUCTIVE PATHWAYS OF THE CORTICAL COLLECTING DUCT

Mineralocorticoids (DOCA) are known to increase Na('+) absorption and K('+) secretion in the rabbit cortical collecting duct (CCD). However, the mechanism of regulation of the apical and basolateral cell membranes and tight junction ion conductive pathways (G('a), G('b), and G('tj), respectively) by mineralocorticoids are only partially understood. Using electrophysiological techniques and microelectrodes it was demonstrated that the apical cell membrane contained a dominant Ba('2+) sensitive K('+) conductive pathway, G(,K)('a), and an amiloride sensitive Na('+) conductive pathway, G(,Na)('a). The basolateral membrane contained a dominant Cl('-) conductive pathway, G(,Cl)('b), and a significant Ba('2+) sensitive K('+) conductive pathway, G(,K)('b). Upon elevating the mineralocorticoid levels of rabbits with intact adrenal glands it was found that V('te) was significantly increased after 1 day with a further increase after 13-16 days. These results indicated both primary and secondary effects of mineralocorticoid elevation. After 1 day of DOCA treatment, G(,Na)('a), I(,Na)('a) and I(,K)('a) increased by more than 2-fold and were maintained at high levels after 13-16 days of DOCA treatment. Secondary (chronic) effects of mineralocorticoids were evident after 4 days or more of DOCA treatment. These included a significant increase in G(,K)('a) from 4.0 to 10.2 mS.cm('-2) and a hyperpolarization of V('b) by -20 mV after 4 days of treatment. After 13-16 days of DOCA treatment V('b) remained hyperpolarized at -98.1 mV and G('tj) decreased from 5.6 to 4.2 mS.cm('-2). The hyperpolarization of V('b) was due to an increase in electrogenic Na('+) pump activity as the pump current, I(,act)('b), increased significantly from 35.7 to 195.2 (mu)A.cm('-2). Whereas net passive K('+) current across the basolateral membrane, I(,K)('b), was near zero in the control group of animals, i.e., K('+) near equilibrium, I(,K)('b) was approximately -40 (mu)A.cm('-2) in chronic DOCA treated animals. These results demonstrate that the initial effect of mineralocorticoid elevation is to increase G(,Na)('a). The ensuing depolarization of the apical membrane increases the driving force for K('+) exit into the lumen. Between 1 and 4 days of elevation, G(,K)('a) more than doubles in magnitude and at the same time the electrogenic activity of the Na('+) pump increases. This results in a hyperpolarization of V('b) which increases the driving force for K('+) uptake from the bath to the cell through a basolateral membrane conductive pathway. After 13-16 days G('tj) decreases thereby serving to maintain high electrochemical gradients across the epithelium. Therefore, the long term effects of mineralocorticoid elevation on the CCD appear to be adaptive mechanisms that serve to maintain high levels of K('+) secretion and Na('+) absorption. ^

Advanced Physical Chemistry Problems (II), Hydrogen Atom and Hyrdrogen Molecular Ion

Slightly advanced problems in Physical Chemistry, herein concerning the H-atom and the Hydrogen Molecular Cation, are presented and discussed.

Perchlorate remediation technologies: A systematic review of solely biodegradation versus a combination of ion-exchange and biodegradation technologies

A systematic review was performed in order to evaluate perchlorate remediation technologies. The two included technologies were ion-exchange concerted with biodegradation and solely biodegradation. A meta-analysis was completed and subsequently, a regression model was formed to conduct a degradation rate analysis and to depict the association between rate and various dependent variables (salinity/sali, nitrate concentration/nitc and carbon source concentration/csou). The outcome of the model analysis suggested that salt concentration did have an effect on the degradation rate in the ion-exchange process and that with a salt concentration greater than or equal to 18.6 g/L, the biodegradation process will produce a greater reduction of perchlorate than ion-exchange concerted with biodegradation. However, when a t-test examined the difference in perchlorate degradation rate between the two cleanup methods, there was no significant difference seen (p=0.7351, α = 0.05).^

Scanned Ion Beam Therapy for Thoracic Tumors

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some patients with Hodgkin lymphoma, carbon-ion therapy would reduce the predicted risk of second cancer incidence in the breast compared with proton therapy. The purpose of this work was to determine whether 4D-optimized carbon-ion therapy would significantly reduce the predicted risk of radiation induced second cancers in the breast for female Hodgkin lymphoma patients while preserving tumor control compared with proton therapy. To achieve our goals, we first investigated whether 4D-optimized carbon beam tracking could reduce dose to volumes outside a moving target compared with 3D-optimized carbon beam tracking while preserving target dose coverage. To understand the reliability of scanned carbon beam tracking, we studied the robustness of dose distributions in thoracic targets to uncertainties in patient motion. Finally, we investigated whether using carbon-ion therapy instead of proton therapy would significantly reduce the predicted risk of second cancer in the breast for a sample of Hodgkin lymphoma patients. We found that 4D-optimized ion beam tracking therapy can reduce the maximum dose to critical structures near a moving target by as much as 53%, compared to 3D-optimized ion beam tracking therapy. We validated these findings experimentally using a scanned carbon ion synchrotron and a motion phantom. We found scanned carbon beam tracking to be sensitive to a number of motion uncertainties, most notably phase delays in tracking, systematic spatial errors, and interfractional motion changes. Our findings indicate that a lower risk of second cancer in the breast might be expected for some Hodgkin lymphoma patients using carbon-ion therapy instead of proton therapy. For our reference scenario, we found the ratio of risk to be 0.77 ± 0.35 for radiogenic breast cancer after carbon-ion therapy versus proton therapy. Our findings were dependent on the RBE values for tumor induction and the radiosensitivity of breast tissue, as well as the physical dose distribution.