Optical control of capacitance in a metal-insulator-semiconductor diode with embedded metal nanoparticles.

This paper describes a metal-insulator-semiconductor (MIS) capacitor with flat capacitance voltage characteristics and a small quadratic voltage capacitance coefficient. The device characteristics resemble a metal-insulator-metal diode except that here the capacitance depends on illumination and exhibits a strong frequency dispersion. The device incorporates Fe nanoparticles (NPs), mixed with SrF2, which are embedded in an insulator stack of SiO2 and HfO2. Positively charged Fe ions induce dipole type traps with an electronic polarization that is enhanced by photogenerated carriers injected from the substrate and/or by inter nanoparticle exchange of carriers. The obtained characteristics are compared with those of five other MIS structures: two based on Fe NPs, one with and the other without SrF2 sublayers. Additionally, devices contain Co NPs embedded in SrF2 sublayers, and finally, two structures have no NPs, with one based on a stack of SiO2 and HfO2 and the other which also includes SrF2. Only structures containing Fe NPs, which are incorporated into SrF2, yield a voltage independent capacitance, the level of which can be changed by illumination. These properties are essential in radio frequency/analog mixed signal applications.

The effect of Fe-coverage on the structure, morphology and magnetic properties of α-FeSi2 nanoislands.

Self-assembled α-FeSi(2) nanoislands were formed using solid-phase epitaxy of low (~1.2 ML) and high (~21 ML) Fe coverages onto vicinal Si(111) surfaces followed by thermal annealing. At a resulting low Fe-covered Si(111) surface, we observed in situ, by real-time scanning tunneling microscopy and surface electron diffraction, the entire sequence of Fe-silicide formation and transformation from the initially two-dimensional (2 × 2)-reconstructed layer at 300 °C into (2 × 2)-reconstructed nanoislands decorating the vicinal step-bunch edges in a self-ordered fashion at higher temperatures. In contrast, the silicide nanoislands at a high Fe-covered surface were noticeably larger, more three-dimensional, and randomly distributed all over the surface. Ex situ x-ray photoelectron spectroscopy and high-resolution transmission electron microscopy indicated the formation of an α-FeSi(2) island phase, in an α-FeSi(2){112} // Si{111} orientation. Superconducting quantum interference device magnetometry showed considerable superparamagnetism, with ~1.9 µ(B)/Fe atom at 4 K for the low Fe-coverage, indicating stronger ferromagnetic coupling of individual magnetic moments, as compared to high Fe-coverage, where the calculated moments were only ~0.8 µ(B)/Fe atom. Such anomalous magnetic behavior, particularly for the low Fe-coverage case, is radically different from the non-magnetic bulk α-FeSi(2) phase, and may open new pathways to high-density magnetic memory storage devices.

Shape-controlled nanopores in single crystals.

Nanometer length-scale holes (nanopores) are often formed in amorphous materials for fundamental studies of molecular mass transport. In the current study, electron beam irradiation in the transmission electron microscope was used to form nanopores in a crystalline material (Si). Analysis of the nanopores showed that they are formed by knock-on of atoms by the high energy incident electron beam, and surface diffusion is partially responsible for the hour-glass shapes that are found for some nanopores. Energetically favorable three-dimensional shapes of nanopores were simulated, and the nanopores simulated in the model crystalline material were found to be more stable than the nanopores simulated in the amorphous material. The nanopore shape was also found to depend on the nanopore diameter-to-length ratio. Based on the above, we demonstrate the advantage in using a crystalline material for nanopore formation and show that control of the three-dimensional shape of nanopores formed by electron beam irradiation is possible.

An experimental method for calibration of the plasmon mean free path.

Transmission electron microscopy specimens in the form of elongated, conical needles were made using a dual-beam focused ion beam system, allowing the specimen thickness to be geometrically determined for a range of thickness values. From the same samples electron energy loss maps were acquired and the plasmon mean free path (lambda) for inelastic scattering was determined experimentally from the measured values of specimen thickness. To test the method lambda was determined for Ni (174 +/- 17 nm), alpha-Al(2)O(3) (143 +/- 14 nm), Si (199 +/- 20 nm) and amorphous SiO(2) (238 +/- 12 nm), and compared both to experimental values of lambda taken from the literature and to calculated values. The calculated values of lambda significantly underestimate the true sample thickness for high accelerating voltages (300 kV) and large collection angles. A linear dependence of lambda on thickness was confirmed for t/lambda < 0.5-0.6, but this method also provides an approach for calibrating lambda at sample thicknesses for which multiple scattering occurs, thus expanding the thickness range over which electron energy loss spectroscopy can be used to determine the absolute sample thickness (t/lambda > 0.6). The experimental method proposed in this contribution offers a means to calibrate lambda for any type of material or phase that can be milled using a focused ion beam system.

Quantitative HRTEM analysis of FIB prepared specimens.

The preparation of good transmission electron microscopy specimens with minimum milling damage can be very complicated, especially from a specific area in a sample. Therefore, a novel approach for transmission electron microscopy specimen preparation using a focused ion beam system is proposed, based on the use of low energy (5 kV)Ga ions and a low incident ion angle (approximately 1 degree ) from a thickness of approximately 500 nm until the sample is electron transparent. Transmission electron microscopy specimens prepared by this method have significantly less irradiation damage, demonstrated by successful quantitative high-resolution transmission electron microscopy conducted on sapphire from data acquired using an aberration-corrected field emission gun transmission electron microscopy. Quantitative analysis was conducted by iterative digital image matching. The accuracy and sensitivity of the matching process is discussed.

Ordered liquid aluminum at the interface with sapphire.

Understanding the nature of solid-liquid interfaces is important for many processes of technological interest, such as solidification, liquid-phase epitaxial growth, wetting, liquid-phase joining, crystal growth, and lubrication. Recent studies have reported on indirect evidence of density fluctuations at solid-liquid interfaces on the basis of x-ray scattering methods that have been complemented by atomistic simulations. We provide evidence for ordering of liquid atoms adjacent to an interface with a crystal, based on real-time high-temperature observations of alumina-aluminum solid-liquid interfaces at the atomic-length scale. In addition, crystal growth of alumina into liquid aluminum, facilitated by interfacial transport of oxygen from the microscope column, was observed in situ with the use of high-resolution transmission electron microscopy.

Prognostic significance of the number of bone scan abnormalities at the time of initial bone metastatic recurrence in breast carcinoma.

BACKGROUND: To gain insight into the factors that contribute to the more favorable prognosis associated with recurrence limited to bone in patients with breast carcinoma, the authors analyzed the number of sites of initial involvement identified on radionuclide bone scans in relation to long term outcome. METHODS: Records of 641 patients with clinical Stage I-III breast carcinoma that originally was diagnosed in 1974-1985 were reviewed. During follow-up, 295 patients (46%) experienced distant recurrence, including 116 with bone as the sole initial site of metastatic disease. Radionuclide bone scans identified the initial site(s) of recurrence in 113 of these latter 116 patients, and these studies were categorized by the number of skeletal lesions subsequently confirmed as metastases (1, 2, or > or = 3). Survival from time of recurrence and time of original diagnosis was analyzed using Kaplan-Meier methods, and factors associated with recurrence and mortality were examined using logistic and Cox regression. RESULTS: Median survival from time of recurrence was 35 months in the patients with bone-only metastases, compared with 11-26 months for all other sites of visceral recurrence exclusive of bone. Number of positive lymph nodes and estrogen receptor status were the only predictive variables for recurrence. Median survival from time of recurrence and time of original diagnosis for the 3 bone scan categories was: 1 lesion (n = 47), 53 and 86 months; 2 lesions (n = 22), 38 and 68 months; and > or = 3 lesions (n = 44), 22 and 58 months (P < 0.0001 and P < 0.005 for 1 and 2 lesions vs. > or = 3). In the "bone-only" group, the number of scan lesions was the strongest predictor of length of survival. CONCLUSIONS: Patients with breast carcinoma who experience a recurrence in bone at only one or two sites initially have a survival advantage over those with more extensive (> or = 3 sites) skeletal metastases and those with metastatic disease involving other visceral organs.

An investigation of lymphatic function following free-tissue transfer.

Despite microsurgical advances in the repair of severed arteries, veins, and nerves, disrupted lymphatics are not usually identified or reconnected during replantation. Although temporary swelling of a replanted part is attributed to lymphedema, this condition resolves without microsurgical intervention. Spontaneous regeneration or reconnection of lymphatics is thought to occur in such situations. Microsurgical free-flap transfer is clinically analogous to replantation in that it also results in a complete division of all lymphatic channels exiting the flap. The ability of lymphatics to regenerate after flap reconstruction, either pedicled or free, has received little attention because safe and accurate techniques for visualization and evaluation of the status of these structures have not been available. As a result of recent advances in radiocolloid lymphoscintigraphic imaging techniques, it is possible to demonstrate lymphatic flow in a physiologic, anatomic, and noninvasive manner. These methods can be applied to free-flap models to document lymphatic function after surgical treatment and determine when and to what extent such a process of growth occurs. We studied 10 consecutive patients having free-flap reconstruction. These flaps were performed for chronic osteomyelitis (6) and unstable wound coverage (4). Microvascular flaps used were latissimus dorsi, scapular-parascapular fasciocutaneous, lateral arm, rectus abdominis, temporoparietal, and free toe. Radiocolloid lymphoscintigraphy with technetium-99m-antimony trisulfide colloid (Sb2S3) was done on all patients by injection directly into the free-flap dermis. All patients were studied between 8 and 44 days (mean 23.6) after free-flap transfer. Following injection into each flap, rapid egress of the radiotracer along lymphatic pathways with progression to locoregional nodes was observed in all patients. Reestablishment of lymphatic pathways following microvascular free-tissue transfer was demonstrated by radionuclide lymphoscintigraphic techniques in 10 consecutive patients who had reconstruction for extremity wounds.

Bone lymphoma. Comparison of Tl-201 and Ga-67 citrate scintigraphy in assessment of treatment response.

Assessment of response to therapy in patients with lymphoma involving bone can be difficult. Of the scintigraphic techniques available, Tl-201 may be the most ideal radiopharmaceutical because it reflects tumor burden more accurately than either Tc-99m MDP or Ga-67 citrate. We compared serial Tl-201 and Ga-67 citrate scintigraphs (24 studies, 12 pairs) in assessing the response to therapy in three patients with non-Hodgkin's lymphoma involving bone. In two patients who demonstrated a complete remission, uptake of Tl-201 diminished more rapidly and returned to normal earlier than did Ga-67 citrate. Tl-201 did not show tumor recurrence in the one patient with lesions shown to be Tl-201 negative at baseline. Serial studies using Tl-201 may be superior to Ga-67 citrate in the evaluation of lymphoma involving bone provided that Tl-201 avidity is demonstrated on baseline studies.

Protection against daunorubicin cytotoxicity by expression of a cloned human carbonyl reductase cDNA in K562 leukemia cells.

Carbonyl reductase (CBR) catalyzes the reduction of daunorubicin (DN) to its corresponding alcohol, daunorubicinol (DNOL), and changes the pharmacological properties of this cancer chemotherapeutic drug. The DN reductase associated with CBR reduces the C13 methyl ketone group and does not metabolize the quinone ring of DN. Reports comparing DN and DNOL toxicity have resulted in various conclusions depending on the cells tested. Differences in toxicity could be due to variations in several enzymes involved in DN metabolism. In this report, the effects of CBR expression on DN metabolism and cell toxicity were determined by cloning and expressing a human CBR cDNA in DN reductase-deficient myeloid erythroleukemia K562 cells. CBR activity increased 83-fold in the K562-transfected cells and was associated with a 2-3-fold reduction in DN toxicity. Maximum protection occurred at 30 nM DN where 94% of the intracellular DN was converted to DNOL within 2 h. The reduced toxicity was specific for DN. Other CBR substrates such as menadione, phenanthrenequinone, and doxorubicin were equally toxic to both the CBR expresser cells and the control cells under the conditions tested. Our results suggest that high levels of CBR in tumor cells could contribute to drug resistance. The results also suggest that reduction of DN to DNOL protects against DN toxicity by altering interaction of the drug at one or more of the many target sites.

Cloning and expression of the cDNA encoding rabbit liver carbonyl reductase.

Two cDNA sequences encoding rabbit carbonyl reductase (CBR) were cloned from a lambda gt10 rabbit liver cDNA library. The rabbit cDNAs coded for a protein with 84% identity to human CBR. Transient expression of the two rabbit cDNA sequences in COS7 cells increased both quinone reductase and aldo-keto reductase activities. These data demonstrate that CBR cDNAs from rabbit and human tissues code for similar proteins.

Changes in Tc-99m radionuclide bone scan images and peripheralization of marrow hematopoietic activity associated with the administration of granulocyte colony stimulating factor as an adjunct to dose-intensified chemotherapy for breast cancer. A case report.

Granulocyte colony stimulating factor (G-CSF) is used clinically for chemotherapy-associated neutropenia. Very little is known about the manner in which pharmacologic dosing of G-CSF may affect radiologic studies in vivo. Dramatic changes on bone scan associated with the administration of G-CSF used to support dose-intensified combination chemotherapy in a patient with metastatic breast carcinoma are described. The scintigraphic findings were correlated histologically with increased hematopoietic activity in the bone marrow located in peripheral bones.

Gallium-67-citrate imaging in extragonadal and gonadal seminomas: relationship to radiologic findings.

METHODS: The results and analysis of baseline and follow-up 67Ga imaging in three patients with extragonadal seminoma were compared to those of nine patients with primary and metastatic gonadal seminomas. Gallium-67 tumor avidity was scored (0-6) relative to accumulation in the sternum and the liver. Response time to systemic therapy for 67Ga imaging compared to other radiological examinations was also measured. RESULTS: Prior to therapy, 67Ga scan sensitivity was 100%, (3/3) in patients with extragonadal seminomas and 90%, (9/10) for primary and radiologically evident metastatic sites in patients with gonadal seminomas. The combined sensitivity was 92%, (12/13) with the smallest 67Ga scan detecting a mass 1.5 cm in diameter. There was no significant difference in 67Ga avidity or sensitivity between extragonadal and gonadal sites. Following chemotherapy, CT scanning demonstrated residual radiologic abnormalities in all three extragonadal seminoma tumor sites and 5/8 metastatic gonadal seminoma tumor sites. However, the 67Ga scan was normal in 10/11 sites at the first radionuclide examination after systemic therapy, indicating no active tumor, an observation supported by clinical follow-up from 6 to 72 mo. CONCLUSION: Gallium-67 scanning appears useful in the management of patients with both extragonadal and gonadal seminoma and may be useful in differentiating active disease from fibrosis in the treated patient with a post-therapy residual radiologic mass.

Healing flare in skeletal metastases from breast cancer.

PURPOSE: To identify the frequency, characteristics, and prognostic significance of scintigraphically detected healing flare in patients with breast cancer metastatic to bone. MATERIALS AND METHODS: Findings on bone scans and concomitant radiographs of 1,188 patients were reviewed. Bone metastases occurred in 426 patients. Outcomes of 101 patients (aged 21-71 years) with skeletal metastases were correlated with typical scintigraphic and radiographic features. RESULTS: Healing flare with increased radiotracer uptake and radiographically demonstrated sclerotic changes in osteolytic or mixed skeletal metastases were prospectively identified in 12% of patients with skeletal metastases. Healing flare was detected 3.2 months +/- 1.4 after initiation of hormonal treatment or chemotherapy. Skeletal metastatic activity stabilized on bone scans within 6.2 months +/- 3.0. Patients with healing flare did not survive longer than patients without healing flare but with stable metastases after treatment (3.3 years +/- 2.0 vs 3.9 years +/- 1.6). CONCLUSION: Scintigraphically detected healing flare represents a favorable response to therapy not associated with increased survival.

Constitutive secretion of soluble interleukin-2 receptor by human T cell lymphoma xenografted into SCID mice. Correlation of tumor volume with concentration of tumor-derived soluble interleukin-2 receptor in body fluids of the host mice.

Increased serum concentration of soluble alpha-chain receptor for interleukin-2 (sIL-2R) has been noted in patients with a variety of inflammatory conditions and lymphoid malignancies including T cell leukemia and lymphoma. Elevated sIL-2R serum levels seen in lymphoid malignancies appear to correlate with the clinical stage of disease. However, because sIL-2R is produced by normal activated lymphocytes, it has been uncertain whether serum sIL-2R in such conditions is derived from tumor cells or normal immune cells responding to the tumor. To address this question, we used a model of human (CD30+) anaplastic, large T cell lymphoma transplanted into immunodeficient SCID mice. Reverse transcription polymerase chain reaction of tumor RNA showed that the tumor, designated mJB6, contains mRNA for alpha-chain of human IL-2R. Furthermore, 15 to 25% of tumor cells stained with anti-human IL-2R alpha-chain mAb. Solid phase ELISA analysis of serum samples from mice bearing mJB6 lymphoma showed high concentrations of human sIL-2R. None of the control mice without lymphoma or with human nonlymphoid tumors (prostatic carcinoma, ovarian carcinoma, and glioblastoma multiforme) showed detectable human sIL-2R. The sIL-2R serum titers of mJB6-bearing mice correlated strongly with tumor volume (P < 0.0001). Tumors as small as 0.4 to 0.8 mm3 could be detected by this method. The sensitivity of sIL-2R ELISA exceeded at least 150 times the sensitivity of conventional radioisotopic tumor detection. Total resection of mJB6 tumors resulted in complete clearance of sIL-2R from the murine serum within 48 hours with a half-life of 6 hours. Accordingly, partial resection led to a significant decrease in sIL-2R followed by gradual increase with tumor regrowth. sIL-2R was also detected in the urine of mJB6-transplanted mice. As in serum, urine concentrations of sIL-2R were proportional to tumor mass (P < 0.02). Based on these findings we postulate that malignant cells are a major source of serum sIL-2R in patients with lymphoid tumors. In addition, our data further support monitoring sIL-2R concentration in body fluids as a sensitive method to detect change in tumor volume in such patients.

Large-cell and immunoblastic lymphoma of the mediastinum: prognostic features and treatment outcome in 57 patients.

PURPOSE: A retrospective study was performed to define clinical characteristics and therapeutic outcome for patients with large-cell and immunoblastic lymphoma of the mediastinum. PATIENTS AND METHODS: Fifty-seven patients who presented with primary, mediastinal large-cell and immunoblastic lymphoma were retrospectively studied to determine initial sites of disease, radiologic characteristics, treatment, outcome, and factors that have prognostic significance for progression-free and overall survival. RESULTS: Fifty-six of the 57 patients had disease that was confined to sites above the diaphragm. Bulky disease and extensive intrathoracic infiltration were common in these patients. All patients were treated with intensive chemotherapy regimens, and 44% of patients received chest irradiation. The overall 5-year survival by Kaplan-Meier estimation was 50% with a freedom-from-relapse rate of 45%. Predictors of disease relapse after chemotherapy included the presence of a pleural effusion (P = .015), a number of involved extranodal sites (P < .01), and a lactic dehydrogenase (LDH) ratio > 3.0 (LDH value/upper limit of assay; P = .04) as well as an incomplete treatment response as evidenced by residual mass on chest radiograph (P = .02) or persistent gallium 67 avidity (P = .01) after chemotherapy. Predictors of decreased survival included the presence of pleural effusion (P = .001), the number of involved extranodal sites (P = .022), and a positive posttreatment 67Ga scan (P = .027). CONCLUSION: Patients with primary mediastinal large-cell and immunoblastic lymphoma have an approximate 50% chance of surviving disease-free after initial therapy. The presence of pleural effusion at presentation was associated with an extremely poor outcome. Bulk disease per se was a negative predictive factor only in patients without pleural effusions when compared with patients who did not have bulk disease. In addition, all patients with involvement of two or more extranodal sites relapsed when treated with standard chemotherapy.

Ga-67 scintigraphy after bone marrow harvest. Significance of "sacroiliac" asymmetry in the lymphoma patient.

The importance of recognizing asymmetric Ga-67 citrate uptake in the sacroiliac region after bone marrow harvest and transplant is discussed in a case of non-Hodgkin's lymphoma. The patient underwent chemotherapy, irradiation, and autologous bone marrow transplant for stage IV disease. Ga-67 scintigraphy revealed sacroiliac asymmetry suggesting medial iliac reparative changes after bone marrow harvest. Iliac bone marrow biopsy showed no evidence of infection or of recurrent tumor. Subsequent follow-up imaging and open biopsy demonstrated lymphomatous invasion of adjacent soft tissue where initial findings were thought to represent benign, postharvest changes.

Gallium imaging in metastatic and recurrent soft-tissue sarcoma.

Fifty-six patients with metastatic or recurrent soft-tissue sarcoma were evaluated by 67Ga-citrate imaging. Prior to entry on the therapy protocol, 52/56 (93%) patients had true-positive 67Ga studies. Two of four patients with liposarcoma, one of twelve with leiomyosarcoma and one with an epithelioid sarcoma had false-negative studies; 89/105 disease sites (85%) were 67Ga positive, including 100% of pleural lesions, 94% in bone, 88% in the abdomen, 85% in soft tissue, 78% in lung parenchyma and 56% of liver metastases. There was significant association between 67Ga avidity and tumor grade with the exception of mesothelioma. No relationship was seen between 67Ga avidity and tumor cell type, disease site or lesion size. Following therapy, 67Ga correctly identified 11/12 sites of active disease in 8/9 patients. Mean pre- and post-therapy 67Ga avidity scores did not differ significantly. Gallium-67 appears to have an important role in the evaluation of patients presenting with either primary or metastatic soft-tissue sarcoma.