Interstitial Distribution Research Articles

Intratumoral Injection of Low-Energy Photon-Emitting Gold Nanoparticles: A Microdosimetric Monte Carlo-Based Model.

Gold nanoparticles (Au NPs) distributed in the vicinity of low-dose rate (LDR) brachytherapy seeds could multiply their efficacy thanks to the secondary emissions induced by the photoelectric effect. Injections of radioactive LDR gold nanoparticles (LDR Au NPs), instead of conventional millimeter-size radioactive seeds surrounded by Au NPs, could further enhance the dose by distributing the radioactivity more precisely and homogeneously in tumors. However, the potential of LDR Au NPs as an emerging strategy to treat cancer is strongly dependent on the macroscopic diffusion of the NPs in tumors, as well as on their microscopic internalization within the cells. Understanding the relationship between interstitial and intracellular distribution of NPs, and the outcomes of dose deposition in the cancer tissue is essential for considering future applications of radioactive Au NPs in oncology. Here, LDR Au NPs (103Pd:Pd@Au-PEG NPs) were injected in prostate cancer tumors. The particles were visualized at time-points by computed tomography imaging ( in vivo), transmission electron microscopy ( ex vivo), and optical microscopy ( ex vivo). These data were used in a Monte Carlo-based dosimetric model to reveal the dose deposition produced by LDR Au NPs both at tumoral and cellular scales. 103Pd:Pd@Au-PEG NPs injected in tumors produce a strong dose enhancement at the intracellular level. However, energy deposition is mainly confined around vesicles filled with NPs, and not necessarily close to the nuclei. This suggests that indirect damage caused by the production of reactive oxygen species might be the leading therapeutic mechanism of tumor growth control, over direct damage to the DNA.

Histopathological evaluation of skin in cirrhotic patients with pruritus

Background: Cirrhosis often is a silent disease Clinical symptoms at presentation may include jaundice of the eyes or skin, pruritus, gastrointestinal bleeding, coagulopathy, increasing abdominal girth, and mental status changes. Pruritus may be the presenting symptom, arising years before any other classic clinical and laboratory markers of hepatic dysfunction. This study examines the clinical, laboratory and histopathological changes in the skins of cirrhotic patients with pruritus in comparison with cirrhotic patients without pruritus and healthy control skins . Patients and Methods: To evaluate clinical, laboratory and histopathological changes in cirrhotic patients with pruritus, cirrhotic patients without pruritus and corresponding healthy (control). skin biopsies (20 specimens each) using hematoxylin and eosin stain and to study mast cell density using gimesa stain. Results: In the skin biopsy specimens of the cirrhotic patients with pruritus we found several histological changes including: epidermal hyperplasia (acanthosis) ,vascular ectasia(dilated dermal blood vessels), hypertrophied dermal nerve endings, mixed inflammatory cellular infilterate and lymphocytic vasculopathy (swelling of the endothelial cell lining of the blood vessels without fibrinoid necrosis, leucocytoclasia or extravasation of red blood cells). Evaluation of mast cell count in Gimesa stained skin sections revealed an increased numbers of these cells in the group of cirrhotic patients with pruritus ( N=5-10). The cells noted in perivascular, perineural and interstitial distribution (between collagen bundles). Conclusions: We report, for the first time, some histopathologial changes in the skins of cirrhotic patients with pruritus in comparison with cirrhotic patients without pruritus and healthy control skins .

The evolution of interaction between grain boundary and irradiation-induced point defects: Symmetric tilt GB in tungsten

Molecular dynamics method is used and scheme of calculational tests is designed. The atomic evolution view of the interaction between grain boundary (GB) and irradiation-induced point defects is given in six symmetric tilt GB structures of bcc tungsten with the energy of the primary knock-on atom (PKA) EPKA of 3 and 5 keV and the simulated temperature of 300 K. During the collision cascade with GB structure there are synergistic mechanisms to reduce the number of point defects: one is vacancies recombine with interstitials, and another is interstitials diffuse towards the GB with vacancies almost not move. The larger the ratio of the peak defect zone of the cascades overlaps with the GB region, the statistically relative smaller the number of surviving point defects in the grain interior (GI); and when the two almost do not overlap, vacancy-intensive area generally exists nearby GBs, and has a tendency to move toward GB with the increase of EPKA. In contrast, the distribution of interstitials is relatively uniform nearby GBs and is affected by the EPKA far less than the vacancy. The GB has a bias-absorption effect on the interstitials compared with vacancies. It shows that the number of surviving vacancies statistically has increasing trend with the increase of the distance between PKA and GB. While the number of surviving interstitials does not change much, and is less than the number of interstitials in the single crystal at the same conditions. The number of surviving vacancies in the GI is always larger than that of interstitials. The GB local extension after irradiation is observed for which the interstitials absorbed by the GB may be responsible. The designed scheme of calculational tests in the paper is completely applicable to the investigation of the interaction between other types of GBs and irradiation-induced point defects.

Atomic Configuration of Point Defect Clusters in Ion-Irradiated Silicon Carbide

Silicon Carbide (SiC) is a promising cladding material for accident-tolerant fuel in light water reactors due to its excellent resistance to chemical attacks at high temperatures, which can prevent severe accident-induced environmental disasters. Although it has been known for decades that radiation-induced swelling at low temperatures is driven by the formation of black spot defects with sizes smaller than 2 nm in irradiated SiC, the structure of these defect clusters and the mechanism of lattice expansion have not been clarified and remain as one of the most important scientific issues in nuclear materials research. Here we report the atomic configuration of defect clusters using Cs-corrected transmission electron microscopy and molecular dynamics to determine the mechanism of these defects to radiation swelling. This study also provides compelling evidence that irradiation-induced point defect clusters are vacancy-rich clusters and lattice expansion results from the homogenous distribution of unrecovered interstitials in the material.

Effect of interstitial carbon distribution and nickel substitution on the tetragonality of martensite: A first-principles study

By using first principles calculations, the effects of carbon distribution and of 25 at.% of nickel substitution on the tetragonality of ferrous martensite have been investigated. Different carbon concentrations have been considered (0≤xc ≤ 12.5 at.%). All calculations were based on the Projector Augmented Wave (PAW) method of the Density Functional Theory (DFT). The Special Quasirandom Structure (SQS) method has been used to model the disordered structures of the Fe16C2X and (Fe,Ni)16C2X systems. Our calculations demonstrate that the lattice parameters a and c vary linearly with carbon concentration, up to the high value of xc = 12.5 at.% (for X = 1). The nickel substitution enhances the expansion of parameter c of the Fe16C2X system up to 37%. This trend is correlated with the shear moduli calculated for bcc-iron and the disordered Fe25 at.%Ni structure. The mixing energies of the Fe16C2X and (Fe,Ni)16C2X systems indicate that the unmixing of martensite by spinodal decomposition is favoured by the nickel substitution. It is shown that carbon-carbon interactions are mostly repulsive until the distance of two bcc-iron lattice parameters.

Aerosol removal and cloud collapse accelerated by supersaturation fluctuations in turbulence

AbstractPrior observations have documented the process of cloud cleansing, through which cloudy, polluted air from a continent is slowly transformed into cloudy, clean air typical of a maritime environment. During that process, cloud albedo changes gradually, followed by a sudden reduction in cloud fraction and albedo as drizzle forms and convection changes from closed to open cellular. Experiments in a cloud chamber that generates a turbulent environment show a similar cloud cleansing process followed by rapid cloud collapse. Observations of (1) cloud droplet size distribution, (2) interstitial aerosol size distribution, (3) cloud droplet residual size distribution, and (4) water vapor supersaturation are all consistent with the hypothesis that turbulent fluctuations of supersaturation accelerate the cloud cleansing process and eventual cloud collapse. Decay of the interstitial aerosol concentration occurs slowly at first then more rapidly. The accelerated cleansing occurs when the cloud phase relaxation time exceeds the turbulence correlation time.

Two-compartment modeling of tissue microcirculation revisited.

Conventional two-compartment modeling of tissue microcirculation is used for tracer kinetic analysis of dynamic contrast-enhanced (DCE) computed tomography or magnetic resonance imaging studies although it is well-known that the underlying assumption of an instantaneous mixing of the administered contrast agent (CA) in capillaries is far from being realistic. It was thus the aim of the present study to provide theoretical and computational evidence in favor of a conceptually alternative modeling approach that makes it possible to characterize the bias inherent to compartment modeling and, moreover, to approximately correct for it. Starting from a two-region distributed-parameter model that accounts for spatial gradients in CA concentrations within blood-tissue exchange units, a modified lumped two-compartment exchange model was derived. It has the same analytical structure as the conventional two-compartment model, but indicates that the apparent blood flow identifiable from measured DCE data is substantially overestimated, whereas the three other model parameters (i.e., the permeability-surface area product as well as the volume fractions of the plasma and interstitial distribution space) are unbiased. Furthermore, a simple formula was derived to approximately compute a bias-corrected flow from the estimates of the apparent flow and permeability-surface area product obtained by model fitting. To evaluate the accuracy of the proposed modeling and bias correction method, representative noise-free DCE curves were analyzed. They were simulated for 36 microcirculation and four input scenarios by an axially distributed reference model. As analytically proven, the considered two-compartment exchange model is structurally identifiable from tissue residue data. The apparent flow values estimated for the 144 simulated tissue/input scenarios were considerably biased. After bias-correction, the deviations between estimated and actual parameter values were (11.2±6.4) % (vs. (105±21) % without correction) for the flow, (3.6±6.1) % for the permeability-surface area product, (5.8±4.9) % for the vascular volume and (2.5±4.1) % for the interstitial volume; with individual deviations of more than 20% being the exception and just marginal. Increasing the duration of CA administration only had a statistically significant but opposite effect on the accuracy of the estimated flow (declined) and intravascular volume (improved). Physiologically well-defined tissue parameters are structurally identifiable and accurately estimable from DCE data by the conceptually modified two-compartment model in combination with the bias correction. The accuracy of the bias-corrected flow is nearly comparable to that of the three other (theoretically unbiased) model parameters. As compared to conventional two-compartmentmodeling, this feature constitutes a major advantage for tracer kinetic analysis of both preclinical and clinical DCE imaging studies.

Tissue Distribution of a Therapeutic Monoclonal Antibody Determined by Large Pore Microdialysis

Therapeutic monoclonal antibodies (mAbs) exhibit limited distribution to the target tissues. Determination of target tissue interstitial concentration of mAbs is an important aspect in the assessment of their pharmacokinetic/pharmacodynamics relationship especially for mAbs targeting membrane bound receptors. The pharmacokinetics of R7072, a full length mAb (IgG) targeting human insulin-like growth factor-1 receptor was evaluated following a single intravenous dose at 1, 6.25, and 25 mg/kg in healthy female SCID-beige mice. R7072 showed linear pharmacokinetics over the dose range tested and was characterized by low systemic clearance and long terminal half-life. Furthermore, interstitial distribution of R7072 was evaluated in liver, skin, kidney, and muscle tissues using large pore microdialysis (MD) after intravenous administration of 10 mg/kg dose in mice. The relative recoveries of R7072 were consistent and similar between in vitro and in vivo MD experiments. The tissue and interstitial concentrations were significantly lower compared to serum concentrations and found to be highest in liver and lowest in muscle. The interstitial concentrations of R7072 were approximately 2-fold to 4-fold lower than corresponding total tissue concentrations. Large pore MD appears to be an attractive approach for direct measurement of pharmacologically relevant concentrations of therapeutic mAbs in tissue interstitial fluid.

CD5-Negative Mantle Cell Leukemia Shows Frequent 17p Deletion and Marrow Involvement Mimicking Marginal Zone Lymphoma

Introduction: Mantle cell lymphoma is characterized by the t(11;14)(q13;q32) and can usually be recognized by its typical CD5+/CD23- immunophenotype. However, phenotypic variations have been observed and such variants can resemble other types of B-cell neoplasms, including chronic lymphocytic leukemia (CLL/SLL) and marginal zone lymphoma. In particular, the CD5- variant is diagnostically challenging. Some CD5- mantle cell lymphomas have been reported to have an indolent clinical course, while others follow an aggressive course similar to typical mantle cell lymphoma. To our knowledge, CD5- mantle cell leukemia has not been fully characterized. To further our understanding of this disease entity for diagnostic workup and risk assessment, we evaluated clinical, morphologic, immunophenotypic, and genetic features in a cohort of CD5- mantle cell leukemia.Methods: Among 111 cases of mantle cell leukemia identified from our database over a 2-year period, 12 were CD5- with t(11;14) and absolute peripheral lymphocytosis (>5,000/uL). Antigen expression was defined by flow cytometry as positive, dim positive, or negative. Conventional chromosome analysis and FISH were performed on all cases, including probes for 11q22.3 (ATM), 12 (CEP 12), 13q14, 13q34, 17p13 (TP53) and t(11;14) (IGH-CCND1). Other parameters obtained included age, gender, CBC, blood and bone marrow histology, and IgVH mutational status.Results: Of the 12 patients, 7 were female with a median age of 67 years (range: 55-88 years). Patients presented with marked lymphocytosis (mean: 55 K/uL) and mild normocytic anemia (mean: 11.3 g/dL). The average platelet count was within the low normal range (mean: 173 K/uL). Flow cytometric analysis showed that all cases expressed CD19 and surface light chain restriction (10 kappa and 2 lambda), and lacked CD5 and CD10. All except one case expressed CD20. CD23 was negative in 8 cases and dim positive in 4 cases. Thus, the leukemic phenotype was suggestive of a marginal zone lymphoma. Morphologically, the leukemic cells were small to medium sized with round nuclei and scant to moderately abundant cytoplasm. Bone marrow biopsy was performed in 6 of 12 cases. All 6 cases showed marrow involvement (mean: 45%; range: 25-85%) with interstitial and intrasinusoidal distribution patterns. While the marrow histology was suggestive of involvement by marginal zone lymphoma, immunohistochemical testing for cyclin D1 revealed positive nuclear staining in the leukemic cells. FISH for t(11;14) was positive in all 12 cases. In contrast, conventional chromosome analysis detected t(11;14) in only 6 cases (3 blood and 3 marrow samples). Additional cytogenetic abnormalities were detected in 8 (67%) patients. Five (42%) cases showed 17p deletion. Other abnormalities included 13q- (3/12; 25%), 11q- (2/12; 17%), and trisomy 12 (1/12; 8%). IgVH analysis was performed in 2 cases, and both exhibited IgVH hypermutation.Conclusions: CD5- mantle cell leukemia comprised approximately 11% of mantle cell leukemia in our series. In addition to t(11;14), other chromosome abnormalities were identified in the majority of the cases (67%). Deletion of 17p was most frequent, likely representing a more aggressive form in contrast to the previously described indolent form. The leukemic immunophenotype and marrow infiltration features resembled marginal zone lymphoma, indicating the importance of detecting t(11;14) for proper classification and clinical management of the disease. We observed that FISH was much more sensitive in detecting t(11;14) than conventional chromosome analysis. Therefore, performing FISH for t(11;14) and 17p- would be useful for diagnostic workup of mature B-cell leukemia regardless of CD5 positivity. Our limited observation of IgVH hypermutation in CD5- mantle cell leukemia would suggest future studies to investigate this potential relationship for prognostic implications. DisclosuresNo relevant conflicts of interest to declare.

Value of Immunohistochemistry-Based Direct Visualization for Localization, Lineage Determination and Monitoring of IDH1 p.R132H Mutant Clones in AML

Abstract Background Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are important prognostic biomarkers in acute myeloid leukemia (AML). Although the clinicopathologic correlates of IDH mutations have been extensively studied, the distribution of abnormal myeloid cells carrying these mutations has not been studied. Specific localization of cells carrying IDH mutations will be useful in further understanding the pathophysiology and post-treatment biology of IDH mutant cases of AML. This characterization is becoming particularly relevant for identification of minimal residual disease, especially for patients treated with novel IDHinhibitors. In this study, we characterized IDH1 p.R132H clones in bone marrow specimens involved by AML using a mutation specific antibody. Materials and Methods Bone marrow tissue sections (biopsy or clot specimens) from 32 AML cases with IDH1 p.R132H mutation were stained with IDH1 p.R132H-mutation specific antibody. These cases include 20 de novoAML and 12 cases of AML with myelodysplasia-related changes (AML-MRC). We also included 10 AML cases with wild-type IDH1 as a control. After confirmation of the positive IDH1 immunohistochemical (IHC) signal in the primary specimens, follow up bone marrow specimens (n=67) including (a) persistent disease, (b) minimal residual disease by flow cytometry, (3) complete remission by morphology and flow cytometry, but, positive for mutation by PCR, as well as (4) relapsed cases after complete remission were included in the study (in progress). We also included pre- and post-treatment (unresponsive with increasing blast counts, stable disease, persistent disease with decreasing blast counts, complete remission, and relapse) bone marrow specimens (n=72) from 16 patients treated with IDH inhibitors (in progress). Results All the IDH1 wild type AML cases were negative for IDH1 IHC stain showing 100% specificity. Positive signal was detected in all de novo AML and AML-MRC (allelic frequency ranges from 1.8% to 47% by PCR) except one AML case with 8.9% allele burden which was a limited sample; overall sensitivity was 96%. The IHC signal was detected in the cytoplasm of myelomonocytic cells, their precursors, and megakaryocytes. Erythroid precursors, lymphoid cells, endothelial cells, and osteoblasts were consistently negative. The signal intensity ranged from weak (n=10) to moderate (n=9), to strong (n=13). The positive cells predominantly showed an interstitial distribution in the bone marrow. In the de novo AML group, only the immature cells were positive in 100% of pre-treatment AML cases. However, both mature and immature cells were positive in 7/13 (54%) post-treatment AML cases (6 cases treated with hypomethylating agents). One case was transformed from MPN which also showed positivity in mature and immature cells. In two cases with complete morphologic remission and one case with minimal residual disease detected by flow cytometry, IHC signal was detected in both mature and immature cells; both patients relapsed in 8 and 11 months. In the AML-MRC group, both immature and mature cells were positive in 11/12 (92%) cases of which 2 were not previously treated indicating the possibility that IDH1 mutation is an early event. Since the remaining 9 patients were treated with hypomethylating agents, the positivity of both mature and immature cells as a result of maturation effect versus an early event cannot be assessed. Additional studies for follow-up AML cases, including cases on an IDH inhibitor clinical trial are in progress. Conclusions Our preliminary data indicate that IDH1 IHC is a highly specific and sensitive tool to detect IDH1 R132H mutated cases and can be used as a primary method to localize the population of mutation-bearing cells in the bone marrow. IHC also allows determination of whether the IDH1 mutation in the post-treatment setting is arising from immature or mature cells. IHC provides an opportunity to understand the difference between these two populations and, based on characterization of cell type and distribution, may be helpful to predict whether the risk of relapse is high. Disclosures DiNardo: Agios: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Celgene: Research Funding; Abbvie: Research Funding.

Increasing minority carrier lifetime in as-grown multicrystalline silicon by low temperature internal gettering

We report a systematic study into the effects of long low temperature (≤500 °C) annealing on the lifetime and interstitial iron distributions in as-grown multicrystalline silicon (mc-Si) from different ingot height positions. Samples are characterised in terms of dislocation density, and lifetime and interstitial iron concentration measurements are made at every stage using a temporary room temperature iodine-ethanol surface passivation scheme. Our measurement procedure allows these properties to be monitored during processing in a pseudo in situ way. Sufficient annealing at 300 °C and 400 °C increases lifetime in all cases studied, and annealing at 500 °C was only found to improve relatively poor wafers from the top and bottom of the block. We demonstrate that lifetime in poor as-grown wafers can be improved substantially by a low cost process in the absence of any bulk passivation which might result from a dielectric surface film. Substantial improvements are found in bottom wafers, for which annealing at 400 °C for 35 h increases lifetime from 5.5 μs to 38.7 μs. The lifetime of top wafers is improved from 12.1 μs to 23.8 μs under the same conditions. A correlation between interstitial iron concentration reduction and lifetime improvement is found in these cases. Surprisingly, although the interstitial iron concentration exceeds the expected solubility values, low temperature annealing seems to result in an initial increase in interstitial iron concentration, and any subsequent decay is a complex process driven not only by diffusion of interstitial iron.

Interstitial Oxide Ion Distribution and Transport Mechanism in Aluminum-Doped Neodymium Silicate Apatite Electrolytes.

Rare earth silicate apatites are one-dimensional channel structures that show potential as electrolytes for solid oxide fuel cells (SOFC) due to their high ionic conductivity at intermediate temperatures (500-700 °C). This advantageous property can be attributed to the presence of both interstitial oxygen and cation vacancies, that create diffusion paths which computational studies suggest are less tortuous and have lower activation energies for migration than in stoichiometric compounds. In this work, neutron diffraction of Nd(28+x)/3AlxSi6-xO26 (0 ≤ x ≤ 1.5) single crystals identified the locations of oxygen interstitials, and allowed the deduction of a dual-path conduction mechanism that is a natural extension of the single-path sinusoidal channel trajectory arrived at through computation. This discovery provides the most thorough understanding of the O(2-) transport mechanism along the channels to date, clarifies the mode of interchannel motion, and presents a complete picture of O(2-) percolation through apatite. Previously reported crystallographic and conductivity measurements are re-examined in the light of these new findings.

Histopathological and Digital Morphometrical Evaluation of Uterine Leiomyoma in Brazilian Women.

The current study aims to evaluate histopathological and digital morphometrical aspects associated with uterine leiomyomas in one hundred and fifty (150) patients diagnosed with leiomyoma. Uterine tissues were subjected to the histopathological and digital morphometric analyses of the interstitial collagen distribution. The analysis of medical records indicates that most of the women diagnosed with uterine leiomyomas (68.7%) are between 37 and 48 years old. As for the anatomic location of the tumors, approximately 61.4% of the patients had intramural and subserosal lesions. In 50% of the studied cases, the patients developed uterine leiomyomatosis (with more than eight tumors). As for the morphometric study, the average size of the interstitial collagen distribution held approximately 28.53% of the capture area, whereas it was of 7.43% in the normal tissue adjacent to the tumor. Another important aspect observed in the current study was the high rate of young women subjected to total hysterectomy, a fact that resulted in early and definitive sterility.

Multi-scale simulations of single particle displacement damage in silicon

Silicon devices are extensively used in space and other radiation-rich environments. They must withstand radiation damage processes that occur over wide range of time and length. Ion implantation technique, one of the most important process in the fabrication of integrated circuits, can also create the displacement damage in silicon lattice. Exposure of silicon wafer or silicon device to radiation causes the creations of variety of defects and has adverse effects on the electrical properties of devices. Although phenomenological studies on the radiation effects in silicon have been carried out in the past decades, the features of multi-scale of displacement damage make it difficult to characterize the defect production and evolution experimentally or theoretically. Recently, the silicon device with ultra-low leakage current was shown to be very sensitive to the permanent displacement damage induced by single particles, called single particle displacement damage (SPDD) event. To the best of our knowledge, the investigation of single particle displacement damage (SPDD) event in silicon device by the coupling molecular dynamics (MD) and kinetic Monte Carlo (KMC) techniques has not yet been reported so far. In this paper, MD simulations are combined with KMC simulations to investigate the formation and evolution of SPDD event in silicon. In MD simulations, Tersoff potential is used to describe the Si-Si atomic interactions. The potential smoothly joins to Ziegler-Biersack-Littmark potential that describes the energetic short range interactions well. All atoms in the MD cell are allowed to evolve 0.205 ns to track the damage production and short-term evolution. A multi-phase simulations are performed to improve the simulation efficiency. Then the nearest neighbor criterion is employed to identify the configurations and spatial distributions of interstitials and vacancies, which are used as input in KMC simulations to study the thermal diffusion and interactions of those defects in the time interval from 0.205 ns to 1000 s. The results show that no defects are missing when transferring from MD to KMC simulation and the whole damage obtained in MD simulations is reproduced in KMC simulations. Since the production and evolution of defects are simulated, the SPDD current could be calculated based on Shockley-Read-Hall theory. We derive the formula to calculate the SPDD current and its annealing factor related to interstitials and vacancies in the depletion region. The calculated annealing factors of defects are compared with the annealing factors of SPDD currents and also with the experimental results. The results show that an annealing factor of defects has the same value as the annealing factor of an SPDD current when only one type of defect is considered in the calculations, while there are some differences between these two annealing factors when two and more types of defects are considered. The annealing factors of defects can be used to represent the annealing behaviors of SPDD currents since the divergences between these two annealing factors are not significant. Finally, SPDD current annealing factor based MD simulation results obtained with Tersoff potential are compared with the results in our previous study in which the Stillinger-Weber potential is used, and also compared with experimental results. The comparisons show that the simulation results with considering both Stillinger- Weber potential and Tersoff potential are in good agreement with experimental results. Compared with the calculated results with considering the Tersoff potential, the results with considering the Stillinger-Weber potential are closer to experimental results.

Dynamics of Interstitial Fluid Pressure in Extracellular Matrix Hydrogels in Microfluidic Devices.

In order to understand how interstitial fluid pressure and flow affect cell behavior, many studies use microfluidic approaches to apply externally controlled pressures to the boundary of a cell-containing gel. It is generally assumed that the resulting interstitial pressure distribution quickly reaches a steady-state, but this assumption has not been rigorously tested. Here, we demonstrate experimentally and computationally that the interstitial fluid pressure within an extracellular matrix gel in a microfluidic device can, in some cases, react with a long time delay to external loading. Remarkably, the source of this delay is the slight (∼100 nm in the cases examined here) distension of the walls of the device under pressure. Finite-element models show that the dynamics of interstitial pressure can be described as an instantaneous jump, followed by axial and transverse diffusion, until the steady pressure distribution is reached. The dynamics follow scaling laws that enable estimation of a gel's poroelastic constants from time-resolved measurements of interstitial fluid pressure.

(Invited) Radiation-Induced Defect Mechanisms in GaN HEMTs

Gallium nitride (GaN) high electron mobility transistors (HEMTs) have been recognized as a key enabling technology for power amplifiers and high power converters for next-generation military and civilian systems. The superiority of GaN over Si benefits applications such as wireless communications, and electronic warfare attack, protection, and support systems. Also, GaN HEMTs also are excellent candidates for applications in radiation intensive environments such as counter weapons of mass destruction system survivability and space systems. The objective is to investigate radiation-induced defects on GaN HEMTs, leading to understanding about the defect formation mechanisms and their impact on performance and reliability of GaN HEMTs. AlGaN/GaN HEMT epitaxial layers were grown on Si substrates by metal organic chemical vapor deposition (MOCVD). The GaN buffer layer is >1 μm and the AlxGa1-xN (x=27%) barrier layer is 17 nm thick. HEMTs were exposed to 2 MeV protons at room temperature in a tandem Van de Graaff accelerator iteratively, up to a fluence of 6 x 1014 H+/cm2. I-V, C-V, and Hall measurements were performed to characterize the radiation-induced changes in HEMT performance, and high-resolution transmission electron microscopy (HRTEM) is used to identify radiation-induced defect mechanisms. Bombardment of 2 MeV protons causes a uniform distribution of vacancies, interstitials, and Frenkel pairs, with minimal larger damage cascades. The stopping range of 2 MeV is much larger than the epitaxial GaN thickness. The AlGaN/GaN interface of an as-fabricated HEMT has an abrupt junction between the AlGaN and GaN. However, after irradiation, atomic recoil of displaced atoms results in intermixing of the AlGaN and GaN layers. The irradiated HEMT has an increased surface roughness. Since the AlGaN/GaN interface is where the two-dimensional electron gas (2DEG) forms, the surface roughness impacts the 2DEG mobility. The Hall mobility measured on Van der Pauw structures begins to degrade at a fluence of 5 x 1013 H+/cm2. This mobility degradation is attributed to the increase in surface roughness between the AlGaN and GaN layers. In addition, TEM analysis revealed where certain threading dislocations exist, that after proton irradiation, Ni from the Schottky Ni gate diffuses down into the dislocation. This impacts the HEMT performance by changing leakage paths, but also, voids were observed in the Ni gate, where the nickel had diffused into the semiconductor at the gate edges. Figure 1

PECULIARITIES OF A DEFECT GENERATION DURING A HEAT TREATMENT OF LARGE DIAMETER DISLOCATION−FREE SILICON WAFERS WITH SPECIFIED DISTRIBUTION OF OXYGEN−CONTAINING GETTERING CENTRES

For this purpose the opportunities of perfect layer formation during RTA have been analyzed in dislocation−free silicon wafers. The RTA application is based on an opportunity of effective influence on a distribution of oxygen precipitate density on wafer thickness by means of control of vacancies and interstitial atoms distributions. However the decision of this important task is connected with an oc-currence of large local wafer stresses concentrated near fastening supports and a significant bend of large diameter Si wafers. Therefore in this project the mathematical modeling of three−dimension strain state and defect formation in large diameter Si wafer were investigated: the various ways of wafer fastening were analyzed and the opportunities of stresses reduction in Si wafers were determined. For the description of RTA defect formation the mathematical model taking into account of diffusion−recombination processes of vacancies and interstitial Si atoms, and also formation of vacancy clusters have been applied. On the basis of this model the time thermal RTA parameters were determinated: heating mode, hold time at the maximal temperature and cooling rate of wafer. They provide a formation of required perfect layer near wafer surface contained the corresponding vacancy concentration and cluster density on wafer thickness. The calculated results have been verified by authors of this project on test samples investigated by Light Microscopy (LM) and Transmission Electron Microscopy (TEM). Detailed LM and TEM researches of microdefect distributions and morphology have been carried out for the experimental Si wafers subjected to various RTA modes and multistage heat treatment in Belarusian plant «Integral».

Modeling interorgan distribution and bioaccumulation of engineered nanoparticles (using the example of silver nanoparticles)

In this paper we demonstrate the validity of a mathematical chamber model to describe the absorption, distribution, and bioaccumulation of nonmetabolizable nanoparticles (NPs) using the example of silver NPs in the organism of laboratory rat. The model is constructed using experimental data on the bioaccumulation and biodistribution of silver NPs of average diameter of 35 ± 15 nm (M ± SD) radiolabeled with 110mAg. In the minimally acceptable form, the model includes all “chambers” in which NP level in the course of the experiment was no lower than 20–25% of its blood content, namely, the gastrointestinal tract (GIT), blood itself, osteomuscular carcass, liver, and spleen. NP bioaccumulation and biodistribution in these chambers is described by five independent linear differential equations of the 1st order. A numerical solution of this system of equations, with account for the data on timing of NP excretion from the GIT in the content of feces, makes it possible to determine the biokinetic rate constants for the interorgan transfer of NPs. These rate constants are used to establish the dose-dependence of the peak (maximum) and quasi-stationary NP content in critical target organs, respectively, in the case of acute (single) and subchronic (repeated) administration of NP in the gastrointestinal tract. The results justify the value of the method of mathematically modeling the interstitial transport and distribution of NPs to assess their potential toxic effects on a system level using previously obtained in vitro data and results from biokinetic studies.

A model for thermal oxidation of Si and SiC including material expansion

A model based on drift-diffusion-reaction kinetics for Si and SiC oxidation is discussed, which takes the material expansion into account with an additional convection term. The associated velocity field is determined self-consistently from the local reaction rate. The approach allows a calculation of the densities of volatile species in an nm-resolution at the oxidation front. The model is illustrated with simulation results for the growth and impurity redistribution during Si oxidation and for carbon and silicon emission during SiC oxidation. The approach can be useful for the prediction of Si and/or C interstitial distribution, which is particularly relevant for the quality of metal-oxide-semiconductor electronic devices.

Mild hyperthermia enhances transport of liposomal gemcitabine and improves in vivo therapeutic response.

Obstructive biological barriers limit the transport and efficacy of cancer nanotherapeutics. Creative manipulation of tumor microenvironment provides promising avenues towards improving chemotherapeutic response. Such strategies include the use of mechanical stimuli to overcome barriers, and increase drug delivery and therapeutic efficacy. The rational use of gold nanorod-mediated mild hyperthermia treatment (MHT) alters tumor transport properties, increases liposomal gemcitabine (Gem Lip) delivery, and antitumor efficacy in pancreatic cancer CAPAN-1 tumor model. MHT treatment leads to a threefold increase in accumulation of 80-nm liposomes and enhances spatial interstitial distribution. I.v. injection of Gem Lip and MHT treatment lead to a threefold increase in intratumor gemcitabine concentration compared to chemotherapeutic infusion alone. Furthermore, combination of MHT treatment with infusion of 12 mg kg(-1) Gem Lip leads to a twofold increase in therapeutic efficacy and inhibition of CAPAN-1 tumor growth when compared to equimolar chemotherapeutic treatment alone. Enhanced therapeutic effect is confirmed by reduction in tumor size and increase in apoptotic index where MHT treatment combined with 12 mg kg(-1) Gem Lip achieves similar therapeutic efficacy as the use of 60 mg kg(-1) free gemcitabine. In conclusion, improvements in vivo efficacy are demonstrated resulting from MHT treatment that overcome transport barriers, promote delivery, improve efficacy of nanomedicines.