Unconventional Spin Relaxation Involving Localized Vibrational Modes in Ho Single-Atom Magnets.

We investigate the spin relaxation of Ho single atom magnets on MgO/Ag(100) as a function of temperature and magnetic field. We find that the spin relaxation is thermally activated at low field, while it remains larger than 1000 s up to 30 K and 8 T. This behavior contrasts with that of single molecule magnets and bulk paramagnetic impurities, which relax faster at high field. Combining our results with density functional theory, we rationalize this unconventional behavior by showing that local vibrations activate a two-phonon Raman process with a relaxation rate that peaks near zero field and is suppressed at high field. Our work shows the importance of these excitations in the relaxation of axially coordinated magnetic atoms.

Local adsorption structure and bonding of porphine on Cu(111) before and after self-metalation.

We have experimentally determined the lateral registry and geometric structure of free-base porphine (2H-P) and copper-metalated porphine (Cu-P) adsorbed on Cu(111), by means of energy-scanned photoelectron diffraction (PhD), and compared the experimental results to density functional theory (DFT) calculations that included van der Waals corrections within the Tkatchenko-Scheffler approach. Both 2H-P and Cu-P adsorb with their center above a surface bridge site. Consistency is obtained between the experimental and DFT-predicted structural models, with a characteristic change in the corrugation of the four N atoms of the molecule's macrocycle following metalation. Interestingly, comparison with previously published data for cobalt porphine adsorbed on the same surface evidences a distinct increase in the average height of the N atoms above the surface through the series 2H-P, Cu-P, and cobalt porphine. Such an increase strikingly anti-correlates the DFT-predicted adsorption strength, with 2H-P having the smallest adsorption height despite the weakest calculated adsorption energy. In addition, our findings suggest that for these macrocyclic compounds, substrate-to-molecule charge transfer and adsorption strength may not be univocally correlated.

Investigating the molecule-substrate interaction of prototypic tetrapyrrole compounds: adsorption and self-metalation of porphine on Cu(111).

We report on the adsorption and self-metalation of a prototypic tetrapyrrole compound, the free-base porphine (2H-P), on the Cu(111) surface. Our multitechnique study combines scanning tunneling microscopy (STM) results with near-edge X-ray absorption fine-structure (NEXAFS) and X-ray photoelectron spectroscopy (XPS) data whose interpretation is supported by density functional theory calculations. In the first layer in contact with the copper substrate the molecules adsorb coplanar with the surface as shown by angle-resolved NEXAFS measurements. The quenching of the first resonance in the magic angle spectra of both carbon and nitrogen regions indicates a substantial electron transfer from the substrate to the LUMO of the molecule. The stepwise annealing of a bilayer of 2H-P molecules sequentially transforms the XP and NEXAFS signatures of the nitrogen regions into those indicative of the coordinated nitrogen species of the metalated copper porphine (Cu-P), i.e., we observe a temperature-induced self-metalation of the system. Pre- and post-metalation species are clearly discriminable by STM, corroborating the spectroscopic results. Similar to the free-base porphine, the Cu-P adsorbs flat in the first layer without distortion of the macrocycle. Additionally, the electron transfer from the copper surface to the molecule is preserved upon metalation. This behavior contrasts the self-metalation of tetraphenylporphyrin (2H-TPP) on Cu(111), where both the molecular conformation and the interaction with the substrate are strongly affected by the metalation process.

Self-metalation of 2H-tetraphenylporphyrin on Cu(111): an x-ray spectroscopy study.

The bonding and the temperature-driven metalation of 2H-tetraphenylporphyrin (2H-TPP) on the Cu(111) surface under ultrahigh vacuum conditions were investigated by a combination of x-ray photoelectron spectroscopy (XPS) and near-edge x-ray absorption fine structure (NEXAFS) spectroscopy with density functional theory calculations. Thin films were prepared by organic molecular beam epitaxy and subsequent annealing. Our systematic study provides an understanding of the changes of the spectroscopic signature during adsorption and metalation. Specifically, we achieved a detailed peak assignment of the 2H-TPP multilayer data of the C1s and the N1s region. After annealing to 420 K both XPS and NEXAFS show the signatures of a metalloporphyrin, which indicates self-metalation at the porphyrin-substrate interface, resulting in Cu-TPP. Furthermore, for 2H-TPP monolayer samples we show how the strong influence of the copper surface is reflected in the spectroscopic signatures. Adsorption results in a strongly deformed macrocycle and a quenching of the first NEXAFS resonance in the nitrogen edge suggesting electron transfer into the LUMO. For Cu-TPP the spectroscopic data indicate a reduced interaction of first-layer molecules with the substrate as demonstrated by the relaxed macrocycle geometry.

Dynamic Data-Driven Finite Element Models for Laser Treatment of Cancer.

Elevating the temperature of cancerous cells is known to increase their susceptibility to subsequent radiation or chemotherapy treatments, and in the case in which a tumor exists as a well-defined region, higher intensity heat sources may be used to ablate the tissue. These facts are the basis for hyperthermia based cancer treatments. Of the many available modalities for delivering the heat source, the application of a laser heat source under the guidance of real-time treatment data has the potential to provide unprecedented control over the outcome of the treatment process [7, 18]. The goals of this work are to provide a precise mathematical framework for the real-time finite element solution of the problems of calibration, optimal heat source control, and goal-oriented error estimation applied to the equations of bioheat transfer and demonstrate that current finite element technology, parallel computer architecture, data transfer infrastructure, and thermal imaging modalities are capable of inducing a precise computer controlled temperature field within the biological domain.

Magnetic remanence in single atoms.

A permanent magnet retains a substantial fraction of its saturation magnetization in the absence of an external magnetic field. Realizing magnetic remanence in a single atom allows for storing and processing information in the smallest unit of matter. We show that individual holmium (Ho) atoms adsorbed on ultrathin MgO(100) layers on Ag(100) exhibit magnetic remanence up to a temperature of 30 kelvin and a relaxation time of 1500 seconds at 10 kelvin. This extraordinary stability is achieved by the realization of a symmetry-protected magnetic ground state and by decoupling the Ho spin from the underlying metal by a tunnel barrier.

Prevention of detrimental effect of cyclosporin A on vascular ingrowth of transplanted pancreatic islets with verapamil.

The revascularization of pancreatic islet clusters transplanted beneath the renal capsule was studied in a syngeneic mouse model. The degree of vascular ingrowth was visualized by in vivo fluorescence microscopy (fluorescein isothiocyanate-dextran) and judged by a semiquantitative method from coded video recordings. The recipients of isografts were divided into four groups, depending on their daily immunosuppressive treatment: 1) none (controls), 2) 15 mg/kg cyclosporin A (CsA), 3) 0.4 mg/kg verapamil + 15 mg/kg CsA, and 4) 20-30 mg/kg methylprednisolone. In control animals, capillary ingrowth was first demonstrated on day 6, followed by progressive vascularization up to day 34. After 6 mo, the vascular architecture was similar to that seen in normal islets in situ. CsA alone significantly decreased vascular ingrowth on day 14 compared with controls (P less than .02). Verapamil prevented the detrimental effect of CsA (P less than .01), probably by improving renal subcapsular blood flow. Methylprednisolone did not affect revascularization compared with control animals at day 14. We conclude that CsA inhibits vascular ingrowth into transplanted pancreatic islets, which is likely to have clinical implications. The prevention of CsA vascular ingrowth inhibition by a calcium antagonist indicates a possible approach to the correction of this problem, particularly when the renal capsule is used as the recipient's transplant site.

In vivo fluorescence microscopy of kidney subcapsular blood flow in mice. Effects of cyclosporine, (NVA2)-cyclosporine, and isradipine, a new calcium antagonist.

The subcapsular kidney microcirculation in mice was observed through a fluorescence microscope, recorded on videotape, and examined for response to infusions of cyclosporine A (CsA) and cyclosporine G (CsG). Coded video recordings were evaluated by a semiquantitative method. CsA infusion (1.6 +/- 0.4 mg/kg/min) induced a nearly complete inhibition of the subcapsular blood flow. At lower infusion rates (0.46 +/- 0.2 mg/kg/min), the blood flow inhibition was less pronounced. CsG infusions at corresponding rates induced significantly less inhibition. Pretreatment with a new calcium antagonist, isradipine (18-20 micrograms/kg bwt), completely prevented the CsA-induced impairment of subcapsular microcirculation. The calcium antagonist, however, did not improve blood flow when administered after induction of inhibition by CsA (16.8 +/- 2.5 mg/kg), emphasizing the importance of pretreatment. This study suggests hypoperfusion due to vasoconstriction as an important pathophysiologic mechanism for CsA-induced nephrotoxicity. CsG, when given at corresponding rates, induced less inhibition of the blood flow. Pretreatment with a calcium antagonist, isradipine, completely prevented a CsA-induced inhibition of blood flow, suggesting a potential value in the prevention of CsA-induced nephrotoxicity.

Protection against cyclosporine-induced impairment of renal microcirculation by verapamil in mice.

Fluorescence microscopy was used to examine the effect of cyclosporine (CsA) infusion on renal subcapsular (cortical) blood flow in 53 living mice, using FITC-dextran (MW: 156,000) as a fluorescent marker. CsA (8-19 mg/kg body weight) given i.v. for 1 min induced complete inhibition of blood flow. A complete standstill of flow was also obtained during a continuous infusion with a rate of 0.8-2 mg/kg/min. With lower infusion rates (0.15-0.23 mg/kg/min), blood flow was partially impaired. In all experiments, the decrease in flow occurred after a 15-25 min delay, suggesting a CsA metabolite or exhaustion of a protective mechanism as the causative agent. Pretreatment with an alpha-blocking agent, phentolamine (1.0 mg/kg), did not prevent the CsA-induced inhibition of blood flow. In contrast, pretreatment with a calcium antagonist, verapamil (0.3-0.4 mg/kg), prevented the impairment of blood flow at low (0.15-0.23 mg/kg/min), and partially at higher (0.8-2.4 mg/kg/min) rates of CsA infusion. Clinical studies are warranted to explore the role of calcium antagonists in the prevention of posttransplant acute cyclosporine-induced nephrotoxicity.

Angiogenesis in cultured and cryopreserved pancreatic islet grafts.

BACKGROUND: The ability of rat pancreatic islets to revascularize after transplantation was examined via in vitro and in vivo imaging of the microvasculature using laser scanning confocal microscopy (LSCM). METHODS: Cultured or cryoprocessed islets were transplanted at the renal subcapsular site in rats. At various time intervals after transplantation, three-dimensional imaging of the graft was performed by LSCM. In vitro studies were conducted via microvascular corrosion casting of the grafted kidney in situations where it was difficult to obtain in vivo confocal data due to surgical complications. The vascular morphology of the islet grafts was evaluated quantitatively via digital image analysis algorithms to determine the morphology of the neovascular ingrowth and the rate of revascularization. RESULTS: In cultured islet grafts, the initiation of angiogenesis was observed within 1 week, characterized by the presence of capillary sprouts, tortuous vessels, and blood vessels with blind ends. The revascularization of the graft was typically completed within 2 weeks and could be distinguished as a network of completely perfused blood vessels consisting of intertwining capillaries, with surrounding arterioles and venules. The angiogenesis process in cryopreserved islet grafts required a longer time period to initiate (approximately 2 weeks), and the revascularization was completed in 1 week after the initiation. CONCLUSIONS: These results successfully demonstrate the potential of the described in vivo and in vitro LSCM techniques to measure the angiogenesis process in pancreatic islet grafts.

Issues in modeling thermal alterations in tissues.

Thermal injury in living tissues is commonly modeled as a rate process in which cell death is interpreted to occur as a function of a single kinetic process. Experimental data indicate that multiple rate processes govern the manifestation of injury and that these processes may act over a broad spectrum of time domains. Injury is typically computed as a dimensionless function (omega) of the temperature time history via an Arrhenius relationship to which numerical values are assigned based on defined threshold levels of damage. However, important issues central to calculation and interpretation of the omega function remain to be defined. These issues include the following: how is temperature identified in time and space within a tissue exposed to thermal stress; what is the biophysical and physiological meaning of a quantitative value for omega; how can omega be quantified in an experimental system; how should omega be scaled between graded levels of injury; and what are the differences in injury kinetics between unit volume- and unit surface area-governed processes of energy deposition into tissue to cause thermal stress? This paper addresses these issues with the goal of defining a more rigorous and comprehensive standard for modeling thermal injury in tissues.

Sensitivity of kidney perfusion protocol design to physical and physiological parameters.

The introduction and removal of cryoprotective agents (CPA) to a kidney via vascular perfusion may induce changes in cell volume that are destructive to the tubular epithelial or capillary endothelial cells as well as causing significant increases in vascular resistance that compromise the perfusion process. A network thermodynamic model of the coupled osmotic, hydrodynamic and elastic properties of the kidney was applied to evaluate the sensitivity of these critical outputs to a set of physiological and perfusion variables. Simulation results suggest that in the design of perfusion protocols for CPAs such as glycerol, it may be advantageous to: (a) select a CPA with as high a cell membrane permeability as possible; (b) increase the concentration of mannitol in the perfusate to about 200 mos/kg, beyond which there is no discernible benefit; (c) when glycerol is the CPA, limit the rate of reduction in the perfusate during removal to 30 mM/min or less; (d) limit the perfusion pressure to 20-30 mm Hg, within the practical constraints of the perfusion system; (e) increase the concentration of impermeant in the perfusate to as high as 400 mos/kg, although it is recognized that this departure from plasma-like composition might impose other problems that are not considered in this model. Further, it was observed that the vascular membrane permeability plays a relatively minor role in controlling cellular osmotic injury and vascular perfusion resistance and is therefore not a critical parameter in the perfusion design process.

Network thermodynamic model of coupled transport in a multicellular tissue--the islet of Langerhans.

Network thermodynamic modeling via bond graphs was used to describe the water and cryoprotectant additive (CPA) transport in a multicellular tissue. The model is presented as a tool to understand the osmotic behavior of the islets of Langerhans when exposed to ternary aqueous solutions containing an electrolyte and a CPA. It accounts for the effects of the location of cells within the tissue and an interstitial matrix, plus differential permeabilities to water and CPA. The interstitial matrix was assumed to be a porous medium able to store the chemical species being transported. Controlled osmotic stress experiments were conducted on isolated rat pancreas islets to measure the transient volumetric response to step-wise changes in dimethyl sulfoxide, Me2SO, concentration. The model provides a tool for predicting the transient volumetric response of peripheral and interior cells and of interstitial tissue, as well as the build up of solute concentration, during addition and removal of CPAs and freezing and thawing protocols. Inverse solution methods were applied to determine values for standard cell membrane permeability parameters Lp, omega and sigma as well as for the interstitial flow conductivities Kw and Kp'.

Measurement of cell volume loss in the liquid region preceding an advancing phase change interface.

It is well understood that the solidification of a solution results in a redistribution of solute in the liquid zone. For the freezing of suspensions of cells it is anticipated that accumulation of solute in the region leading a growing ice phase will cause an osmotic response in cells before the ice phase reaches the cells. To measure this phenomenon in a specific algal species, the volume changes in Chlorococcum texanum during freezing were studied using directional solidification cryomicroscopy. The relative cell volume was tracked continuously as a function of temperature and position as cells encountered the moving phase front. The loss of cell volume was measured in the liquid region containing concentrated solute ahead of the growing solid phase.

Prediction of transient temperature fields and cumulative tissue destruction for radio frequency heating of a tumor.

A therapeutic hyperthermia protocol using a radio frequency (rf) electrode placed adjacent to a bronchial wall tumor has been modeled using the finite element technique. Variable physical properties and variable blood perfusion have been assigned to the tumor and to the surrounding normal lung tissue. The Laplace equation was solved on a curvilinear grid for a single rf source electrode to determine the steady-state electric field, which in turn governs the energy deposition function. The heat generation in the tumor and in the lung tissue is then calculated from the energy deposition profile, and the bioheat equation is solved on the same finite element mesh to determine the transient temperature history. The temperatures are displayed as isothermal contours at designated times during the protocol and as temperature histories at selected points. In addition, an Arrhenius-type injury model has been implemented to predict thermally induced damage, from which equal total amounts of energy are deposited into the tissue using a constant power density for an appropriate time or using a cyclic heating pattern. The cyclic heating pattern consisted of a series of equal duration time periods during which the rf current source is alternately turned on and off (50% duty cycle). This study illustrates how a finite element model could be used to evaluate alternative protocols for heating a tumor of a specific geometry and to evaluate thermally induced damage to surrounding normal tissue.

Network thermodynamic analysis of vasomotion in a microvascular network.

The modulation of microvascular blood flow by vasomotion in the individual vessels of a simple vascular network was simulated by means of a network thermodynamic model. The flow is driven under a pulsating pressure through two arcades of branching vasoactive arterioles into a passive resistance representing the capillary and venular beds. Each vessel was assumed to have the capability of decreasing rhythmically the local diameter over a short section by a specified fraction of the maximum value and to change the average diameter along its total length in response to alterations in intraluminal pressure. Blood was assumed to exhibit a simple linear viscous flow resistance. Alterations in flow rate and distribution through the network were determined as a function of the magnitude and frequency of vasomotion within the individual arterioles supplying blood to the microvascular bed. Specific cases are shown to illustrate how blood flow can be influenced by the patterns of vasomotion within the network.

Analysis of burns caused by long-term exposure to a heating pad.

The potential for creating a second-degree burn by extended exposure to an electric heating pad was evaluated in a simple model. Extrapolation of empirical results from experiments in thermal burns and in hyperthermia indicated that a heating pad at the low power setting can produce a burn within a threshold time of approximately 12 to 20 hours.

Development and solution of finite-difference equations for burn injury with spreadsheet software.

This article presents a brief description of a set of equations by which the thermal burn process may be modeled, a formulation of the differential equations into a finite-difference format, and a simple method of solution using a standard commercial spreadsheet software application. A companion article provides a discussion of results that can be obtained with the modeling techniques presented here. A short version of the spreadsheet program is available from the author.

Modeling thermal skin burns on a personal computer.

Mathematic models have been used for several decades to predict the severity of burn injury that would result from application of a given thermal stress to the surface of the skin. Solution of the governing mathematic equations has been achieved either by analytic methods, with required simplifying assumptions that may compromise the rigor with which the results are applied, or by numeric methods, which require programming of finite element or finite difference codes in computer languages. In recent years microcomputer hardware and the associated software have become both powerful and relatively simple to use, and the price per unit of computing capability has dropped dramatically. Thus it is now possible to perform on a desktop machine with relative case calculations that previously might have been prohibitively complex or expensive. Modeling of burn injuries fits into this category. This article presents a straightforward method for implementing a finite difference solution to the burn process through the combination of a Macintosh personal computer and a widely used spreadsheet software program; this hardware and software combination has been used widely for a broad spectrum of general computing activities. This article presents a model for a surface thermal burn, as implemented for solution on a spreadsheet, with example runs to illustrate and verify the method.

The effects of epinephrine, ibuprofen, and tetrachlorodecaoxide on cutaneous microcirculation in thermally injured hamsters.

Fluctuations in the diameter of selected arterioles in the cutaneous microcirculation of Syrian golden hamster dorsal skin flap chambers, which ranged in size from 10 to 70 microns at different branching order sites, were measured before burn, at the same sites after burn and after injection of the drug. Three different drugs epinephrine (administered intravenously), ibuprofen (administered intravenously), and tetrachlorodecaoxide (administered intravenously and topically) were evaluated. Results show that the response to thermal injury in the control group involved extensive vasodilation in the arterioles, prolonged flow irregularities including flow obstructions and stasis, and a decrease in the level of vasoactivity of the microvessels. In two treatment groups, the ibuprofen and tetrachlorodecaoxide groups, significant improvement as indicated by reduced vasodilation and edema and improved microcirculatory blood flow after injury were observed. Further testing of tetrachlorodecaoxide as a topically applied wound dressing is indicated.